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Biomedical subjects

J D Berger

Publications and source records attributed to J D Berger.

At least 19 recordsLinked to original sources
PubMed1996

Neuroradiologic applications of central nervous system SPECT.

Single photon emission computed tomography (SPECT) of the central nervous system (CNS) has many potentially useful interventional neuroradiologic applications. CNS SPECT allows easy and safe evaluation of the collateral circulation during internal carotid balloon test occlusion. The cerebrovascular distribution of intracarotid amobarbital sodium, which is used in the Wada test, can be accurately determined with simultaneous injection of a radiopharmaceutical. Easy and safe evaluation of the extent and distribution of vasospasm associated with subarachnoid hemorrhage or cerebral angiography is also possible with CNS SPECT. Images obtained after administration of acetazolamide can be compared with baseline images to evaluate cerebrovascular reserve before carotid endarterectomy. Seizure foci can be identified if peripheral intravenous injection is performed during an ictus. Thallium-201 imaging can be used to direct stereotactic brain biopsy to check for tumor recurrence. Radiologists need to familiarize themselves and their clinical colleagues with the many uses of this imaging technique.

Aged↗
PubMed1995

Isolation of the cell cycle control gene cdc2 from Paramecium tetraurelia.

The polymerase chain reaction was used to amplify a cdc2 homologous sequence from Paramecium tetraurelia. The corresponding amino acid sequences exhibits about 50% similarity to the cdc2 proteins of other species. The Paramecium cdc2 encoded protein is 11 amino acids longer than S. pombe p34cdc2. There is one amino acid change in the conserved PSTAIRE region. Southern blot analysis indicates that Paramecium has multiple cdc2 genes. Northern blotting results shows that Paramecium cdc2 is much more expressed in actively dividing cells. It is almost undetectable in starved stationary cells. The mRNA level of cdc2 gene does not change during the vegetative cell cycle.

Amino Acid Sequence↗
PubMed1993

Radiopharmaceutical therapy of 5T33 murine myeloma by sequential treatment with samarium-153 ethylenediaminetetramethylene phosphonate, melphalan, and bone marrow transplantation.

BACKGROUND: Total-body irradiation, followed by hematopoietic system rescue by bone marrow transplantation (BMT), has been found to improve the response of patients with multiple myeloma to treatment with melphalan. The problems of nonhematopoietic toxicity from whole-body irradiation might be circumvented by using a bone-seeking radiopharmaceutical, such as samarium-153 ethylenediaminetetramethylene phosphonate (153Sm-EDTMP), to ablate the bone marrow. PURPOSE: A mouse model system for multiple myeloma was used to evaluate the potential therapeutic efficacy of sequential therapy with 153Sm-EDTMP, melphalan, and BMT. METHODS: Female C57BL/KaLwRij mice were inoculated with 8 x 10(5) 5T33 murine myeloma cells. Treatment protocols were begun 3 or 10 days later, when the myeloma was either confined to bone marrow or disseminated in liver, spleen, and lymph nodes, simulating human multiple myeloma. 153Sm, a potent beta particle-emitting radioisotope of short half-life (46.7 hours), was linked to the bone-seeking chelate EDTMP. Animals in the first treatment group were each given 22.5 MBq 153Sm-EDTMP via the jugular vein (day 3 or 10), followed by 18.5 mg/kg melphalan (maximum tolerated dose) given intraperitoneally 5 days later (day 8 or 15) and syngeneic BMT another 2 days later (day 10 or 17). Survival in groups of six to 10 animals for each time series was compared with that in mice left untreated (control cohort), in mice treated with 153Sm-EDTMP alone (day 3 or 10), or in mice treated with melphalan alone (day 8 or 15). The hematopoietic systems of animals in the latter two treatment groups recovered full function, obviating the necessity of BMT. The end point was onset of paraparesis, at which time the animals were immediately killed by carbon dioxide asphyxiation. RESULTS: Median survival in untreated control animals was 23 days in those with localized disease and 24 days in those with disseminated myeloma. Treatment with 153Sm-EDTMP alone improved survival to a median of 29 days when commenced on day 3 and 30 days when begun on day 10. Melphalan treatment alone improved the median survival to 31 days for animals with localized myeloma and 34 days in animals with disseminated disease. Additional improvement in survival to a median of 42 days was achieved in animals treated 3 days after tumor inoculation with sequential 153Sm-EDTMP, melphalan, and BMT; median survival was 40 days using this regimen in animals with disseminated myeloma. CONCLUSIONS: Animals in all three treatment protocols survived longer than those left untreated after inoculation with myeloma cells (P < .001). Sequential treatment with 153Sm-EDTMP, melphalan, and BMT was significantly more effective than single-agent treatment (P < .01). No evidence of radiotoxicity was detected in nonhematopoietic organs. IMPLICATIONS: The survival advantage conferred by our sequential treatment protocol suggests its potential clinical usefulness in the treatment of multiple myeloma and other hematologic malignancies in humans.

Animals↗
PubMed1992

A model of multiple myeloma: culture of 5T33 murine myeloma cells and evaluation of tumorigenicity in the C57BL/KaLwRij mouse.

The 5T33 multiple myeloma is one of a series of transplantable murine myelomas arising spontaneously in C57BL/KaLwRij mice. This study describes the establishment and characterisation of the 5T33 murine myeloma in vitro as a cultured cell line in terms of its morphology, growth rate, expression of paraprotein (IgG2b) and tumorigenicity in syngeneic animals. The 5T33 cell line has been in continuous culture for over 10 months and has achieved more than passage 34. In culture, 5T33 myeloma grows as single cells or in small clusters of loosely adherent cells on an adherent stromal cell layer. Maximum doubling time is approximately 25 h, and over 90% of the cells express cytoplasmic IgG2b paraprotein. The cultured 5T33 myeloma cells are highly tumorigenic in C57BL/KaLwRij mice with as few as 500 cells inducing paralysis and death as early as day 36 post-tumour inoculation. Kinetics of tumour development and detection of IgG2b paraprotein are dose dependent. Two weeks following intravenous inoculation of 5 x 10(5) cultured 5T33 myeloma cells, tumour cells were readily identified in the bone marrow. By 3 weeks post-tumour inoculation, 5T33 myeloma cells were found in various tissues throughout the animal. Studies are now underway to determine the sensitivity of this cell line to various therapeutic modalities.

Animals↗
PubMed1992

153Sm-EDTMP and melphalan chemoradiotherapy regimen for bone marrow ablation prior to marrow transplantation: an experimental model in the rat.

Chemoradiotherapy with melphalan and 153Sm-ethylenediaminetetramethylene phosphonate (EDTMP) was used to ablate bone marrow in WAG rats which were subsequently rescued by marrow transplantation. Internal irradiation of bone marrow with high doses of up to 3.5 GBq kg-1 153Sm-EDTMP alone produced profound, but self-limiting, myelosuppression and all animals recovered spontaneously. Melphalan alone in doses of 9.5 mg kg-1 also caused transient myelosuppression without mortality. However, the combination of 9.5 mg kg-1 melphalan and 555 MBq kg-1 153Sm-EDTMP caused marrow ablation and death in 80% of animals. The mortality of this chemoradiotherapy regimen was reduced to 7% by sequential administration of 153Sm-EDTMP on day 0 and melphalan on day 5 followed by marrow transfusion of 7.5 x 10(7) cells on day 6. These results were comparable to those obtained following bone marrow transplantation 24 h after lethal total body external beam irradiation. In the inbred WAG rat experimental model the sequential chemoradiotherapeutic regimen of internal irradiation with 153Sm-EDTMP followed by chemotherapy with melphalan was demonstrated to ablate bone marrow effectively whilst preserving the capacity for recovery following marrow transplantation.

Animals↗
PubMed1991

Timing of oral morphogenesis and its relation to commitment to division in Paramecium tetraurelia.

The interval between commitment to division and fission in synchronous cell samples is a constant fraction of the cell cycle (0.2) in cell cycles up to 6.5 h in duration. In longer cell cycles this interval has a fixed duration of about 80 min. The point of commitment to division is associated with the six-rowed analage stage of oral primordium development (stage V). At this stage cells carrying the cc1 mutation are not blocked by transfer to restrictive conditions but rather proceed to division. Stage V is also the stabilization point for oral anlagen. When shifted to restrictive conditions prior to this stage, development is arrested and resorption of analgen is initiated. The cc1 mutation also blocks contractile vacuole duplication and migration under restrictive conditions. The cc1 gene function is required continuously prior to the transition point. The timing of morphogenetic stages in asynchronous cells is roughly similar to that in synchronous cells. There are, however, significant differences in timing as estimated by the two experimental procedures.

Animals↗
PubMed1990

Commitment to autogamy in Paramecium blocks mating reactivity: implications for regulation of the sexual pathway and the breeding system.

Commitment to autogamy blocks mating reactivity in Paramecium. Cells which had previously developed mating reactivity, lost reactivity 30-90 min prior to the preautogamous fission. Mating reactivity develops at a standard level of starvation when cells are allowed to exhaust their food supply naturally. In abruptly starved cultures, mating reactivity appears 3.3 h after downshift. Autogamy is also triggered by starvation. The level of starvation required for initiation of autogamy decreases progressively as cells age. When the autogamy starvation threshold drops to such a low level that all cells become committed to autogamy before any of them develop mating reactivity, reactivity does not occur under natural starvation conditions and the period of maturity for conjugation has come to an end. There is no absolute immature period for autogamy.

Animals↗
PubMed1989

Commitment to division in Paramecium: effect of nutrient level on the macronuclear DNA increment.

In Paramecium, a fixed macronuclear DNA increment is associated with commitment to cell division. This study shows that this threshold DNA increment is about 70% of the final DNA increment in well-fed cells. The DNA increment is reduced when growth rate is decreased and decreases in parallel with growth rate to a minimum of 30% of the normal DNA increment. This minimum value is obtained when the growth rate is 20% of its normal level or lower. Further reduction in the growth rate produces no further reduction in the DNA increment. Following abrupt nutrient-level shifts, both the threshold DNA increment and the final DNA increment change progressively as the time of the shift is moved to later stages of the cell cycle. The threshold DNA increment is reset following nutrient-level shifts up to the point of commitment to division. These observations are consistent with the notion that the magnitude of the threshold DNA increment is strongly correlated with the rate of growth and is rapidly reset by factors which alter the growth rate. The implications of these observations for growth-driven regulation of the cell cycle are discussed.

Animals↗
PubMed1988

The timing of initiation of DNA synthesis in Paramecium tetraurelia is established during the preceding cell cycle as cells become committed to cell division.

The timing of initiation of DNA synthesis (IDS) in Paramecium is established before cell division at a point located at about 0.75 in the preceding cell cycle. This point occurs about 90 min prior to fission and coincides with the point at which cells become committed to cell division. The location of the point at which the timing of IDS is set was deduced from a series of nutrient-shift experiments. Changes in nutrient level lead to changes in the duration of the subsequent G1 interval when they occur more than 90 min prior to fission. Perturbation of the cell cycle so that the timing of commitment to cell division is altered, results in a parallel shift in the point at which the timing of IDS is established.

Animals↗
PubMed1986

The timing of initiation of macronuclear DNA synthesis is set during the preceding cell cycle in Paramecium tetraurelia. Analysis of the effects of abrupt changes in nutrient level.

In many eukaryotic organisms, initiation of DNA synthesis is associated with a major control point within the cell cycle and reflects the commitment of the cell to the DNA replication-division portion of the cell cycle. In Paramecium, the timing of DNA synthesis initiation is established prior to fission during the preceding cell cycle. DNA synthesis normally starts at 0.25 in the cell cycle. When dividing cells are subjected to abrupt nutrient shift-up by transfer from a chemostat culture to medium with excess food, or shift-down from a well-fed culture to exhausted medium. DNA synthesis initiation in the post-shift cell cycle occurs at 0.25 of the parental cell cycle and not at either 0.25 in the post-shift cell cycle or at 0.25 in the equilibrium cell cycle produced under the post-shift conditions. The long delay prior to initiation of DNA synthesis following nutritional shift-up is not a consequence of continued slow growth because the rate of protein synthesis increases rapidly to the normal level after shift-up. Analysis of the relation between increase in cell mass and initiation of DNA synthesis following nutritional shifts indicates that increase in cell mass, per se, is neither a necessary nor a sufficient condition for initiation of DNA synthesis, in spite of the strong association between accumulation of cell mass and initiation of DNA synthesis in cells growing under steady-state conditions.

Animals↗
PubMed1986

Control of cell division in Paramecium tetraurelia. Effects of abrupt changes in nutrient level on accumulation of macronuclear DNA and cell mass.

In the cell cycle of Paramecium there are three points of interaction between cell growth-related processes and the processes of macronuclear DNA replication and cell division: initiation of DNA synthesis, regulation of the rates of growth and DNA accumulation, and initiation of cell division. This study examines the regulation of the latter two processes by analysis of the response of each to abrupt changes in nutrient level brought about either by transferring dividing cells from a steady-state chemostat culture to medium with unlimited food, or by transferring well-fed dividing cells to exhausted medium. The rates of DNA accumulation and cell growth respond quickly to changes in nutrient level. The amounts of these cell components accumulated during the cell cycle following a shift in nutrient level are typical of those occurring during equilibrium growth under post-shift conditions. Commitment to division occurs at a fixed interval prior to fission that is similar in well-fed and nutrient-limited cells. Initiation of cell division in Paramecium is associated with accumulation of a threshold DNA increment, whose level is largely independent of nutritive conditions. The amount of DNA accumulated during the cell cycle varies with nutritional conditions because the rates of growth and DNA accumulation are affected by nutrient level; slowly growing cells accumulated relatively little DNA during the fixed interval between commitment to cell division and fission.

Animals↗
PubMed1986

Autogamy in Paramecium. Cell cycle stage-specific commitment to meiosis.

Autogamy is a process of meiosis and fertilization which takes place in unpaired Paramecium cells, and which is triggered by starvation. This study examines the consequences of nutritional down-shift at various points within the cell cycle on the occurrence of autogamy. It shows that cells become committed to autogamy in a two-step process. An initial point of commitment to autogamy occurs about 100 min prior to the median time of cell division (cell cycle duration, 330 min). Cells which have become committed to autogamy initiate meiosis following the next fission, others complete another vegetative cell cycle before undergoing meiosis. Treatments that perturb the cell cycle and displace the point of commitment of division also displace the point of initial commitment to autogamy to the same extent. The initial commitment to autogamy can be reversed by refeeding. The second, final, point of commitment to autogamy occurs about 30 min after the fission, immediately prior to initiation of meiosis, and coincides with the beginning of meiosis. If cells are refed at this point, or at later stages, autogamy continues. Autogamy is not well synchronized either in naturally starved cultures or in those subjected to abrupt nutritional down-shift. This is a consequence of the cell cycle stage dependence of entry into autogamy. Autogamy occurs synchronously in samples of dividers selected from asynchronous cultures 2 or more hours after nutritional down-shift. The timing of the events of conjugation and autogamy coincide when the pre-autogamous fission is aligned temporally with the initial contact of mating cells.

Animals↗
PubMed1986

Effects of increased cell mass and altered gene dosage on the timing of initiation of macronuclear DNA synthesis in Paramecium tetraurelia. Implications for cell cycle regulation.

In Paramecium, cell mass and macronuclear DNA content can vary substantially, and both variables affect the timing of initiation of macronuclear DNA synthesis. Cells normally begin macronuclear DNA synthesis at 0.25 in the cell cycle when the mean cell mass is about 119% of the initial value. Gene mutations were used to alter cell size by temporarily blocking cell cycle progression and to change DNA content by altering the segregation pattern of macronuclear material to daughter nuclei at fission. Changes in cell mass or macronuclear DNA content imposed at fission or in the subsequent G1 interval do not affect the timing of initiation of DNA synthesis in that cell cycle, but do affect the timing of initiation of DNA synthesis in the subsequent cell cycle. The progeny of cells with lower than average macronuclear DNA content tend to initiate DNA synthesis earlier than other cells. The G1 interval is proportionally shortened when initial cell mass is greater than normal, and no measurable G1 interval is present when initial cell mass equals or exceeds the normal cell mass present at initiation of DNA synthesis. These results suggest that the timing of initiation of DNA synthesis is established during the preceding cell cycle and that the 'timer' mechanism is not significantly affected by either drastic changes in gene dosage or gene concentration during the G1 interval.

Cell Cycle↗
PubMed1984

A gene function required for cell cycle progression during the G1 portion of the cell cycle and for maintenance of macronuclear DNA synthesis in Paramecium tetraurelia.

The ccl mutation in Paramecium tetraurelia reversibly and rapidly blocks cell cycle progression and DNA synthesis at the restrictive temperature. Progression through the cell cycle is blocked during both the G1 and S portions of the cell cycle, while at the restrictive temperature there is neither residual cell cycle progression nor induction of excess delay of subsequent cell cycle events. DNA synthesis activity is reduced to 50% of the normal level in about 5 min and is completely blocked at 30 min after a shift to restrictive temperature. On return to permissive conditions, DNA synthesis is reactivated with similar kinetics.

Animals↗
PubMed1982

Downward regulation of cell size in Paramecium tetraurelia: effects of increased cell size, with or without increased DNA content, on the cell cycle.

Two temperature-sensitive cell-cycle mutants were used to generate abnormally large cells (size estimated by protein content) with either normal or increased DNA contents. The first mutant, cc1, blocks DNA synthesis, but allows cell growth at the restrictive temperature. The cells do not progress through the cell cycle while at the restrictive temperature, but do recover and complete the cell cycle when returned to permissive conditions. The progeny have increased cell size and normal DNA content. Downward regulation of cell size occurs during the ensuing cell cycle at permissive temperature. Two processes are involved. First, the G1 period is reduced or eliminated. As initial cell size increases there is a progressive shortening of the cell cycle to 75% of normal. This limit cell-cycle duration is reached when the initial mass of the cell is equal to or greater than that of normal cells at the time of DNA synthesis initiation (0.25 of a cell cycle). Cells with the limit cell cycle begin macronuclear DNA synthesis immediately after fission. The durations of the S period and fission are normal. Second, the rate of cell growth is unaffected by the increase in cell size, and results in the partitioning of excess cell mass between the daughter cells at the next fission. The second mutant, cc2, blocks cell division, but allows DNA synthesis to occur at a reduced rate so that cells with up to about 140% of the normal initial DNA content and twice the normal cell mass can be produced. The pattern of cell-cycle shortening is the same as in ccl. The rates of growth and both the rate and amount of DNA synthesis are proportional to the initial DNA content. This suggests that the rates of growth and DNA synthesis are limited by the transcriptional activity of the macronucleus in both cc1 and cc2 cells when they begin the cell cycle with experimentally increased cell mass. Increases in both cell size and initial DNA content are required to bring about increases in the rates of growth and DNA accumulation.

Animals↗