Physician shortage areas and policies to influence practice location.

Our intention is to examine the common assumption that physician supply is related strongly to more direct measures of economic shortage. The concept of a medical shortage defined by untreated illness or excess rates of preventable illness is not considered here. We examine the more policy-specific issue of whether the present shortage areas include the most extreme areas, based on these indicators of market tightness. If supply is a poor predictor of shortage, then more direct measures or other more carefully targeted policies should be explored.

Litter deficits of socially stressed and low status hamster dams.

The effects of maternal social stress, induced by pairing pregnant females, and social status, measured by agonistic behavior within pairs, on pup development was investigated in hamsters. Using litters from untreated first pregnancies as a control, 40 dams were housed either alone or paired with another dam during their second pregnancy. Within a pair, the dam with more aggressive and fewer defensive responses than the other was considered dominant. Compared to their first unpaired litters, second litters of paired dams were smaller in number. Comparisons among second litters showed that paired dams, especially submissive dams, had fewer pups than unpaired dams. It was concluded that both maternal social stress and low status increase intrauterine mortality.

Maternal social stress disrupts reproduction of hamsters drinking high-calorie fluids.

Adding maternal social stress, induced by housing in pairs, to maternal consumption of high-calorie fluids adversely affected hamster reproduction. Pregnancy outcomes of 67 dams housed either alone or in pairs, and given either water (WAT), or isocaloric solutions of either 30% ethanol (ETH), sucrose (SUC) or propylene glycol (PG), were compared. Pups of unpaired dams drinking any high-calorie fluid weighed less than those drinking water, but no other deficits were found. Among paired dams, those designated submissive on the basis of agonistic behavior and drinking either SUC, ETH, or PG, had fewer viable pups and more fetal resorptions and stillborn pups than WAT dams. Also, dominant PG dams delivered few pups and both dominant and submissive PG dams delivered malformed pups or embryos. Whether paired or unpaired, litters of SUC and ETH dams were similar. Drinking any high-calorie fluid reduced maternal food and fluid intake and weight gains below that of water, but pairing had no additional effect on dams.

Retirement against the demographic trend: more older people living longer, working less, and saving less.

The American population is aging rapidly and individuals are living longer. Yet Americans are saving less and older workers are leaving the labor force at younger and younger ages. The accelerated drop in labor force participation corresponds roughly to the introduction of Social Security and the adaptation of employer-provided pension plans. I have illustrated that Social Security and employer-provided pension plans provide substantial incentive to leave the labor force early. The quantitative effect of this inducement is illustrated by simulating the effects of changes in pension plan and Social Security provisions on the retirement decisions of employees in a large firm, who are covered by a typical defined benefit pension plan. Scheduled Social Security changes would have little effect on the retirement decisions of employees with a typical defined benefit pension plan like the one considered here. But if the pension plan provisions were changed to correspond to the Social Security changes, the effect would be very large. And, although not contemplated by current legislation; it is clear that an increase in the Social Security early retirement age would have a substantial effect on the early retirement rates of the large number of employees not covered by a pension plan.

Cytokinesis in cells undergoing mitosis without genome replication.

Chinese hamster ovary cells can be forced to enter mitosis without prior DNA replication by treatment with hydroxyurea and caffeine. Cells treated in this way assemble a spindle that functions normally except that it does not accomplish anaphase spindle elongation (anaphase B). The chromatin detaches from the unreplicated kinetochores, which fragment, but establish microtubule attachments and migrate to the metaphase plate. Partitioning of the kinetochore fragments ensues on the normal schedule. Typical midbodies and cleavage furrows are established and daughter cells of equal size are produced. These results imply that intact chromosomes are not necessary for correct cleavage furrow placement but that kinetochores might be. Further, it is clear that cleavage furrow placement does not depend on anaphase spindle elongation.

Omnibus: a comprehensive Drosophila experiment for the genetics teaching laboratory.

A comprehensive laboratory exercise for the beginning genetics student is presented. The student is given "unknown" Drosophila stocks that carry assorted genetic markers and chromosomal rearrangements. These are crossed inter se in order to illustrate all of the basic genetic phenomena. During the exercise the student learns to proceed from data to conclusion, not vice versa.

Antikinetochore antibodies interfere with prometaphase but not anaphase chromosome movement in living PtK2 cells.

Injection of CREST antikinetochore antiserum (AKA) containing antibodies to the kinetochore into living prometaphase PtK2 cells decreased chromosome velocity to near zero. Injection of either phosphate-buffered saline or CREST antiserum without antikinetochore antibodies (antikinetochore negative: AKN) had no effect on prometaphase oscillations. AKA antiserum injected into anaphase cells at the beginning of chromatid separation had no effect on anaphase chromosome velocity, spindle elongation, or cytokinesis. Visible binding of antikinetochore antibodies in prometaphase cells at room temperature occurred between 5 and 15 minutes after injection. Anaphase cells injected at the beginning of chromatid separation had bound antibody at the end of anaphase. AKA antiserum recognizes in Western blots proteins associated with the primary constriction: CENP-B, -C, and -D, as reported by other workers. The control antiserum, AKN, does not recognize these proteins. These results imply that the antigens recognized by CREST antibodies are important for chromosome movement. Whether or not these antigens are themselves motor molecules cannot be addressed by the present data. In addition, the results suggest that these antigens are not involved in an important way in anaphase movement.

On the mechanism of homologous synapsis in lycosid spiders.

Lycosid spiders have 13 pairs of telocentric chromosomes and 2 nonhomologous sex chromosomes in males. At leptotene, the kinetochore ends are attached to the nuclear envelope via thickened attachment plaques. Homologous synapsis begins at the attachment plaques and proceeds zipper-like through the length of the synaptonemal complex. We have tested whether or not this simple form of homologous synapsis is obligatory by inducing reciprocal translocations. Since we find many irradiated cells with quadrivalents at diakinesis-prometaphase and metaphase I, clearly a backup system exists that can bring together homologous segments disparate from each other in the nucleus. This mechanism apparently does not depend on end-initiated synapsis. Furthermore, we have found in previous studies that wolf spider bivalents are always unichiasmate, with either proximally or distally placed chiasmata. Since many chain quadrivalents, but no ring quadrivalents, were seen in this study, crossing over and chiasma placement obey a different set of rules when homologous segments are switched between chromosomes.

Mitosis in cells with unreplicated genomes (MUGs): spindle assembly and behavior of centromere fragments.

Chinese hamster ovary (CHO) cells, which are arrested at the G1/S-phase of the cell cycle with hydroxyurea, enter mitosis prematurely when treated with caffeine [Schlegel and Pardee, 1986; Science 233-1264-1266]. Such mitotic cells with unreplicated genomes (MUGs) can assemble a mitotic spindle and progress through M-phase even in the absence of intact, replicated chromosomes [Brinkley et al., 1988: Nature 336:251-254; Zinkowski et al., 1991: J. Cell Biol. 113:1091-1110; Christy et al., 1995: Protoplasma 186:193-200]. In order to better define the role of the spindle in chromosome movement, we compared the structure and assembly of mitotic spindles and analyzed the nature of kinetochore association and movement in control cells and MUGs. The mitotic spindles in MUGs display the same morphological features and dynamic properties of assembly-disassembly as seen in normal spindles. Although multiple centromere-kinetochore fragments (CKFs), derived from fragmented chromosomes, interact with and attach to spindle microtubules in both orthodox and unorthodox ways, they nevertheless become aligned on the metaphase plate. Prometaphase congression and alignment at metaphase is achieved in MUGs even though CKFs represent kinetochore fragments that originate from unreplicated chromosomes and, therefore, lack "sister kinetochore" orientation such as seen in chromosomes of control cells. Our study supports the notion that much of the "information" needed for prometaphase chromosome movement and alignment is endemic to the spindle.

Microinjection into crane-fly spermatocytes.

We were successful in microinjecting fluorescently labelled material into crane-fly spermatocytes. In our experiments, we obtained four results. (i) In most attempts, the membrane stretched around the micropipette and prevented entry of fluorescent material, even when the micropipette appeared to be pushed completely through the cell. This confirms suppositions from earlier micromanipulation experiments that the elastic membrane prevents the micropipette needle from entering the cell. (ii) In some attempts, cells lysed upon contact with the micropipette. (iii) In other attempts, we successfully injected fluorescent material into cells. (iv) Fluorescent material left the cells after injection, often passing into adjacent cells. Although our success rate is low, microinjection into crane-fly spermatocytes is indeed possible.

Monogenic inheritance of cyclodiene insecticide resistance in mosquitofish, Gambusia affinis.

Certain populations of the mosquitofish, Gambusia affinis, developed high levels of resistance to endrin and other cyclodiene insecticides as a result of inadvertent exposure to agricultural sprays. Genetic crossing studies show that endrin resistance is inherited as a single, autosomal, intermediate gene.

Orientation of nonrandomly segregating sex chromosomes in spermatocytes of the flea beetle, Alagoasa bicolor L.

In males of the flea beetle, Alagoasa bicolor L., spermatocytes have two achiasmate sex chromosomes, X and Y, each of which is approximately five times larger than the ten pairs of chiasmate autosomes. At metaphase I, these univalent sex chromosomes are located on a spindle domain separated from the autosomal spindle domain by a sheath of mitochondria. A single centriole pair is located at each pole of the spindle. In prometaphase I, each sex chromosome appears to maintain an attachment to both spindle poles via kinetochore microtubules (i.e., amphitelic orientation). Before anaphase I, this orientation changes to the syntelic orientation (both sister kinetochores connected to the same pole), perhaps by the release of microtubule attachments from the more distant pole by each of the chromosomes. The syntelic orientation just prior to anaphase I leaves each sex chromosome attached to the nearest pole via kinetochore microtubules, ensuring nonrandom segregation. As the sex chromosomes reorient, the autosomes follow in a sequential manner, starting with the bivalent closest to the sex spindle domain. We report here data that shed new light on the mechanism of this exceptional meiotic chromosome behavior.

Social and psychological changes after tubal sterilization: A reevaluation study on 425 women.

Four hundred and twenty-five women replied to a questionnaire designed to assess social and psychological changes occurring after tubal sterilization. Dissatisfaction with the outcome of the operation was unrelated to patient age at the time of the operation, parity, religious affiliation and history of emotional instability. While the incidence of negative social and psychological changes was low, a substantial proportion of the sample reported positive effects, particularly in emotional and sexual adjustment.