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Seasonal and yearly population dynamics of two exotic helminths, Camallanus coti (Nematoda) and Bothriocephalus acheilognathi (Cestoda), parasitizing exotic fishes in Waianu Stream, O'ahu, Hawaii.

Exotic poeciliid fishes introduced into Hawaiian freshwaters are responsible for the introduction of several exotic parasites, of which the most important are Camallanus cotti and Bothriocephalus acheilognathi in terms of potential disease threat to native stream fishes. This roundworm and tapeworm are the most prevalent and abundant freshwater fish helminths in Hawaiian streams. This study examined the seasonal and yearly population structure of C. cotti and B. acheilognathi to determine if the tropical Hawaiian environment characterized by low climatic variability permits continuous opportunities for parasite transmission regardless of time of year. Camallanus cotti displayed seasonal differences in prevalence and mean abundance, whereas B. acheilognathi did not. Camallanus cotti prevalence and mean abundance were higher in the Hawaiian summer (47.7%, 0.79) than in winter (25.8%, 0.36). A seasonal relationship of C. cotti levels is likely explained by extensive rains associated with the Hawaiian winter season, which may act to decrease parasite transmission by flushing infected poeciliid hosts, intermediate copepod hosts, and possibly free-living infective worm stages downstream. Bothriocephalus acheilognathi displayed low prevalence and mean abundance in both summer (4.0%, 0.06) and winter (6.5%, 0.07), and it may be difficult to detect seasonal changes due to these low levels. Camallanus cotti prevalence and mean abundance remained relatively constant from the summer of 1995 to the summer of 1999, indicating that levels of this roundworm are stable in Waianu Stream. Whereas B. acheilognathi prevalence and mean abundance were low during the summer of 1995 and the summer of 1997, a dramatic peak in prevalence and mean abundance was observed in the summer of 1998 (41.2%, 1.06), with levels decreasing sharply in the summer of 1999 (4.4%, 0.07). It appears that B. acheilognathi also is present in stable populations at low levels, even though levels rose sharply during a single year.

Animals↗

The epidemiology of diabetes in Swedish children 0-14 years--a six-year prospective study.

Since 1 July 1977, all newly diagnosed diabetic children in Sweden aged 0-14 years have been reported to a central register. During the first 6 years, 2300 newly diagnosed diabetic children out of a population of 1.6 million children were registered. The degree of certainty was close to 100%. The mean of the yearly incidence rate for the whole 6 year period was 23.6 per 100000. The prevalence of insulin dependent diabetes mellitus on 1 July 1980 was 1.48 per 1000 and 1.52 on 1 July 1983. Comparing the first and second 3-year periods, an increase was found (22.7-25.1 per 100000). This increase was consistent when analyzing incidence rates by age, sex, and geographical distribution. Cumulative incidence rates revealed a risk of developing diabetes by the age of 15 years of 3.6 per thousand for boys and 3.2 per thousand for girls. The higher incidence for boys was consistent throughout the study period. Seasonal variations in the incidence rate were also consistent, showing yearly incidence peaks in the autumn and winter months. Incidence peaks were noted for both sexes in the pubertal ages. Age- and sex-standardized morbidity ratios varied significantly within the country. 12.8% of the probands had a first degree relative with Type 1 diabetes, and it was twice as common that this relative was a father as a mother. The high and rapidly increasing incidence of Type 1 diabetes in a genetically stable population such as Sweden calls for case-control studies directed towards the identification of environmental pathogens.

Adolescent↗

A systematic review of the frequency and prognosis of arteriovenous malformations of the brain in adults.

By systematically reviewing the literature, we have found that there is very little information about the frequency and clinical course of arteriovenous malformations (AVMs) of the brain in adults because the methods of most studies have been flawed, and AVMs tend to be treated once they are discovered. The incidence of AVMs is approximately 1 per 100 000 per year in unselected populations, and the point prevalence in adults is approximately 18 per 100 000. AVMs account for between 1 and 2% of all strokes, 3% of strokes in young adults, 9% of subarachnoid haemorrhages and, of all primary intracerebral haemorrhages, they are responsible for 4% overall, but for as much as one-third in young adults. AVMs are far less common causes of first presentations with unprovoked seizures (1%), and of people presenting with headaches in the absence of neurological signs (0.3%). At the time of detection, at least 15% of people affected by AVMs are asymptomatic, about one-fifth present with seizures and for approximately two-thirds of them the dominant mode of presentation is with intracranial haemorrhage. The limited high quality data available on prognosis suggest that long-term crude annual case fatality is 1-1.5%, the crude annual risk of first occurrence of haemorrhage from an unruptured AVM is approximately 2%, but the risk of recurrent haemorrhage may be as high as 18% in the first year, with uncertainty about the risk thereafter. For untreated AVMs, the annual risk of developing de novo seizures is 1%. There is a pressing need for large, prospective studies of the frequency and clinical course of AVMs in well-defined, stable populations, taking account of their prognostic heterogeneity.

Adult↗

Turnover of rat brain perivascular cells.

Brain perivascular spaces harbor a population of cells which exhibit high phagocytic capacity. Therefore, these cells can be labeled by intraventricular injection of tracers. Such perivascular cells at the interface between blood and brain are believed to belong to the monocyte/macrophage lineage and to be involved in antigen presentation. Currently, it is unclear whether these cells undergo a continuous turnover by entering and leaving the bloodstream. Using bone-marrow-chimeric animals, migration of donor macrophages into brain perivascular spaces has been reported. On the other hand, following intracerebral injection of india ink into nontransplanted animals, ink-labeled perivascular cells were still found 2 years after injection, suggesting a high stability of this cell pool. Thus, the turnover of perivascular cells observed in chimeras might be a result of bone marrow transplantation rather than a physiological occurrence. To address this issue, we monitored de novo invasion of macrophages into perivascular spaces of apparently healthy adult rats by applying techniques other than bone marrow transplantation, (i) consecutive injections of different tracers and (ii) ex vivo isolation of macrophages from the blood, cell labeling, and reinjection into the same animal to avoid MHC mismatch. Both approaches revealed vivid de novo invasion of macrophages into perivascular spaces, but not into brain parenchyma, rendering untenable the concept of perivascular cells forming a stable population of macrophages in the brain. Thus, brain perivascular spaces are under permanent immune surveillance of blood borne macrophages in normal adult rats.

Animals↗

Leprosy in Mpumalanga Province, South Africa--eliminated or hidden?

In South Africa, leprosy has been a notifiable condition since 1921. Although the WHO elimination target of less than one case per 10,000 population has been achieved at country level, the distribution of leprosy in the country is distinctly heterogeneous, with a prominent 'leprosy belt' of greater prevalence stretching across Mpumalanga Province into northern Kwa-Zulu Natal. The highest prevalence in this 'belt' has historically been in Ermelo District. Recent trends of few newly detected leprosy patients in this district raised concerns that health system changes may have resulted in failure to detect leprosy cases. Thus a large-scale community awareness campaign was conducted followed by an intensively advertised screening programme of 3-month duration at schools and central gathering points in villages and farms from 1 June to 31 August 2000. One thousand one hundred and seventy-seven people presented for clinical screening at designated points, while 790 scholars were screened at schools and an additional 1433 people were screened at their homes by the field team. Forty-four people with skin or nervous system lesions compatible with leprosy were referred for specialized assessment and biopsy where indicated. Four new leprosy patients were diagnosed, including an elderly lady with pronounced disability. Two of these patients had prior contact with the health service due to dermatological manifestations of leprosy without diagnosis being made. All patients provided a history of close prolonged contact with known leprosy patients. Ongoing intense tracing and follow-up of close contacts of proven leprosy cases may be a more efficient method of detecting leprosy cases in areas with relatively stable populations that have accomplished 'leprosy elimination', than resource intensive community surveys.

Adult↗

Hormonal profile of women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland birth cohort 1966 study.

The hormonal profiles of nested female patients (n = 500) with self-reported symptoms typical of polycystic ovary syndrome (PCOS), oligomenorrhea, and/or hirsutism and their randomly selected controls (n = 1026) at the age of 31 yr were analyzed in a general population-based Northern Finland birth cohort 1966 to find out whether the symptomatic women also have the endocrine characteristics of PCOS and could be detected in a general population using simple questions. Higher medians of serum testosterone (T) (2.10 vs. 1.90 nmol/liter, P < 0.001), LH (5.40 vs. 4.85 U/liter, P = 0.005), insulin (53.8 vs. 51.66 pmol/liter, P = 0.040), and free androgen index (FAI) (4.01 vs. 3.03, P < 0.001) and lower glucose/insulin ratio (91.1 x 10(8) vs. 94.9 x 10(8), P = 0.048) and SHBG (52.4 vs. 60.7 nmol/liter, P < 0.001) were observed among the cases, but no difference was observed in cortisol and glucose levels between the cases and controls. Of all the women in the cohort, 10.2% reported only oligomenorrhea and had biochemical findings similar to the whole case group. Those who reported only hirsutism (10.4%) were in between the case and control groups according to biochemical findings. The subjects who reported both oligomenorrhea and hirsutism (3.4%) had the highest T, LH, FAI, insulin, and glucose and the lowest SHBG and glucose/insulin ratio, compared with the case group and the groups with either symptom only indicating a dose-response manner in typical endocrine profile of PCOS by adding up symptoms. The levels of T and FAI were higher and SHBG lower in groups with overweight or obesity both at 14 and 31 yr, compared with groups with normal weight at 14 yr and overweight or obesity at 31 yr. In the group with normal weight at 14 and 31 yr and the group with overweight or obesity at 14 yr but normal weight at 31 yr, the levels of T and FAI were lowest and SHBG highest. T and FAI were higher and SHBG lower among the cases than the controls in groups stratified by weight development from adolescence to adulthood. In conclusion, this longitudinal study of a large, stable population indicates that women with self-reported symptoms of hirsutism and/or oligomenorrhea show endocrine characteristics of PCOS and can be detected in a general population using simple questions. These symptoms are markers of the underlying metabolic alterations possibly associated with increased health risks in later life.

Adult↗

Irish study on high-density schizophrenia families: field methods and power to detect linkage.

Large samples of multiplex pedigrees will probably be needed to detect susceptibility loci for schizophrenia by linkage analysis. Standardized ascertainment of such pedigrees from culturally and ethnically homogeneous populations may improve the probability of detection and replication of linkage. The Irish Study of High-Density Schizophrenia Families (ISHDSF) was formed from standardized ascertainment of multiplex schizophrenia families in 39 psychiatric facilities covering over 90% of the population in Ireland and Northern Ireland. We here describe a phenotypic sample and a subset thereof, the linkage sample. Individuals were included in the phenotypic sample if adequate diagnostic information, based on personal interview and/or hospital record, was available. Only individuals with available DNA were included in the linkage sample. Inclusion of a pedigree into the phenotypic sample required at least two first, second, or third degree relatives with non-affective psychosis (NAP), one whom had schizophrenia (S) or poor-outcome schizo-affective disorder (PO-SAD). Entry into the linkage sample required DNA samples on at least two individuals with NAP, of whom at least one had S or PO-SAD. Affection was defined by narrow, intermediate, and broad criteria. The phenotypic sample contained 277 pedigrees and 1,770 individuals and the linkage sample 265 pedigrees and 1,408 individuals. Using the intermediate definition of affection, the phenotypic sample contained 837 affected individuals and 526 affected sibling pairs. Parallel figures for the linkage sample were 700 and 420. Individuals with schizophrenia from these multiplex pedigrees resembled epidemiologically sampled cases with respect to age at onset, gender distribution, and most clinical symptoms, although they were more thought-disordered and had a poorer outcome. Power analyses based on the model of linkage heterogeneity indicated that the ISHDSF should be able to detect a major locus that influences susceptibility to schizophrenia in as few as 20% of families. Compared to first-degree relatives of epidemiologically sampled schizophrenic probands, first-degree relatives of schizophrenic members from the ISHDSF had a similar risk for schizotypal personality disorder, affective illness, alcoholism, and anxiety disorder. With sufficient resources, large-scale ascertainment of multiplex schizophrenia pedigrees is feasible, especially in countries with catchmented psychiatric care and stable populations. Although somewhat more severely ill, schizophrenic members of such pedigrees appear to clinically resemble typical schizophrenic patients. Our ascertainment process for multiplex schizophrenia families did not select for excess familial risk for affective illness or alcoholism. With its large sample ascertained in a standardized manner from a relatively homogeneous population, the ISHDSF provides considerable power to detect susceptibility loci for schizophrenia.

Adult↗

Pediatric hypertension. A challenge for pediatricians.

The efforts of physicians involved in the early detection and treatment of hypertension in children and adolescents will be greatly enhanced with the recent publication of the National Heart, Lung, and Blood Institute's Task Force on Blood Pressure Control in Children. Although little is known regarding the relationship of hypertension in childhood and later cardiovascular morbidity and mortality, such preventive efforts toward controlling hypertension should not be delayed. In addition, the availability of distribution curves in children based on repeated observations, and using phase V of Korotkoff sound for the diastolic blood pressures, would be particularly helpful during the transition period from childhood to adolescence. Prospective studies in children in areas of relatively stable population and from the different parts of the world will promote our understanding of pediatric hypertension.

Adolescent↗

Immunogenicity and efficacy of a killed hepatitis A vaccine in day care center children.

The objective of this study was to characterize the immune response of children after the use of two different vaccine doses and to evaluate whether vaccination benefits children attending day care centers in areas with high anti-HAV seroprevalence. The study was conducted in a day care center with a stable population in São Paulo, Brazil. Two groups of 20 children, all seronegative for hepatitis A antibodies, were assigned randomly to receive three times 0.5 and 1.0 ml of the vaccine, the second and third dose 1 and 6 months after the first dose, respectively. There were 27 children in the control group. All children in both vaccinated groups had protective levels of antibodies in the serum after two inoculations, and serious adverse reactions were not observed. In the eighth month of follow-up, a hepatitis A outbreak occurred in the day care center. Five children in the control group had high titers of IgM class anti-HAV, four with clinical manifestations of acute hepatitis. None of the vaccinated children developed symptoms or signs of hepatitis (P = 0.0125), and the estimate of vaccine efficacy was 100%. Two nonstudy children from the center also had clinical and serological evidence of acute hepatitis A. It is concluded that vaccination represents an important method for prevention of hepatitis A transmission in day care centers. The results of this pilot study justify further testing in larger groups.

Child Day Care Centers↗

Establishment and characterization of adenoviral E1A immortalized cell lines derived from the rat suprachiasmatic nucleus.

Primary cultured cells from the presumptive anlage of the rat suprachiasmatic nucleus (SCN) were immortalized by infection with a retroviral vector encoding the adenovirus 12S E1A gene. After drug selection, the resulting neural cell lines (SCN1.4 and SCN2.2) displayed (a) extended growth potential without evidence of transformed or tumorigenic properties, (b) expression of E1A protein within all cell nuclei, and (c) heterogeneous cell types in various stages of differentiation. A large proportion of the SCN1.4 and SCN2.2 cells were characterized by gliallike morphologies, but showed limited expression of corresponding cell type-specific antigens. In addition, both lines exhibited a stable population of cells with neuronlike characteristics. When treated so as to enhance differentiation, these cells were often distinguished by fine, long processes and immunocytochemical expression of neuronal markers and peptides found within SCN neurons in situ. Observations on SCN neuropeptide immunostaining, content, release, and mRNA expression followed a concordant pattern in which somatostatin and vasopressin cells were the most and least common peptidergic phenotypes in both lines, respectively. Since these results indicate that constituents of E1A-immortalized lines derived from the primordial SCN can differentiate into cells with phenotypes resembling parental peptidergic neurons, it will be critical to explore next whether these lines also retain the distinctive function of the SCN to generate circadian rhythms. Cloning of immortalized cell types could subsequently yield useful tools for studying the development of SCN glial and peptidergic cell types and delineating their distinct roles in mammalian circadian time-keeping.

Adenovirus E1A Proteins↗

Epidemiology of Wegener's granulomatosis in northern Norway.

OBJECTIVE: To determine if changes in the incidence, prevalence, and clinical presentation of Wegener's granulomatosis (WG) have occurred in the stable population of northern Norway during a 15-year period. METHODS: We performed a retrospective cohort study using hospital discharge records from all 11 hospitals in the region and the databases of the 2 pathology departments in the area. Only patients fulfilling the American College of Rheumatology 1990 criteria for WG were included in the study, and demographic and clinical data at diagnosis were recorded. Incidence, point prevalence, and period prevalence rates were estimated for three 5-year periods. RESULTS: Fifty-five patients (62% male) with a median age at diagnosis of 50 years (range 10-84 years) fulfilled the inclusion criteria. The annual incidence/ million population increased from 5.2 (95% confidence interval [95% CI] 2.7-9.0) during 1984-1988 to 12.0 (95% CI 8.0-17.3) during 1994-1998. The point prevalence/million increased from 30.4 (95% CI 16.6-51.0) to 95.1 (95% CI 69.1-129.0). The highest incidence rate occurred in men ages 65-74 years. There were no significant period differences in age, first organ involved, delay of diagnosis, or disease activity, but fewer patients had malaise and renal insufficiency during the earliest time period. No seasonal variation in the onset of WG was present, although we noted a pattern of annual fluctuation. CONCLUSION: The prevalence of WG has tripled in northern Norway over the last 15 years. While more efficacious therapy may explain part of this increase, we also found a significant trend toward increased incidence over that period. The incidence rate over the last 5 years is the highest reported so far, while the clinical presentation has remained unchanged.

Adolescent↗

Pattern matching of age-at-death distributions in paleodemographic analysis.

Model age-at-death distributions are generated from fertility and mortality rates derived from two present-day, traditional human societies with widely differing cultural systems: the !Kung hunters-and-gatherers and Yanomamo horticulturalists. Visual examination of these models demonstrates that fertility has more of an effect than mortality on the overall configuration of the age-at-death distributions of stable populations. Comparisons with a late prehistoric Oneota skeletal sample from the American Midwest illustrate how reference age-at-death schedules can be used 1) to identify whether a given skeletal sample approximates an age-at-death distribution expected of an extant human population and 2) to provide a basis for developing further testable hypotheses about the demographic and cultural characteristics of past populations.

Africa, Central↗

The power of regeneration and the stem-cell kingdom: freshwater planarians (Platyhelminthes).

The great powers of regeneration shown by freshwater planarians, capable of regenerating a complete organism from any tiny body fragment, have attracted the interest of scientists throughout history. In 1814, Dalyell concluded that planarians could "almost be called immortal under the edge of the knife". Equally impressive is the developmental plasticity of these platyhelminthes, including continuous growth and fission (asexual reproduction) in well-fed organisms, and shrinkage (degrowth) during prolonged starvation. The source of their morphological plasticity and regenerative capability is a stable population of totipotent stem cells--"neoblasts"; this is the only cell type in the adult that has mitotic activity and differentiates into all cell types. This cellular feature is unique to planarians in the Bilateria clade. Over the last fifteen years, molecular studies have begun to reveal the role of developmental genes in regeneration, although it would be premature to propose a molecular model for planarian regeneration. Genomic and proteomic data are essential in answering some of the fundamental questions concerning this remarkable morphological plasticity. Such information should also pave the way to understanding the genetic pathways associated with metazoan somatic stem-cell regulation and pattern formation.

Animals↗

Dynamics of a fluorescent calmodulin analog in the mammalian mitotic spindle at metaphase.

We have compared the exchange kinetics of fluorescein-labeled calmodulin and tubulin in the spindles of living mitotic cells at metaphase. Cultured mammalian cells in early stages of mitosis were microinjected with labeled calmodulin or tubulin and returned to an incubator to allow equilibration of the fluorescent protein with the endogenous protein pools. Calmodulin becomes concentrated in the mitotic spindle, and treatments with inhibitors of tubulin assembly show that this concentration is dependent on the presence of microtubules. The steady-state exchange rates of both tubulin and calmodulin were measured by an analysis of fluorescence redistribution after photobleaching (FRAP), using cells pre-equilibrated to either 26 +/- 2 degrees C or 36 +/- 2 degrees C. A pulse of laser light focused to a 5-microns diameter column was used to destroy the fluorescence at one pole of a metaphase mitotic spindle. Ratios of fluorescence intensity from the two half-spindles and from the two polar regions were calculated for each image in a post-bleach time series to determine the rates and extents of FRAP. For tubulin, we confirm earlier observations concerning the temperature dependence of the extent of FRAP, but our data do not show a significant temperature dependence for the rate of FRAP. We hypothesize that the reduced extent of tubulin FRAP at the lower temperatures is a result of microtubules that are stable to depolymerization at 26 degrees C and are thus less likely to exchange subunits. Calmodulin's FRAP, however, does not exhibit any of the temperature dependence observed with fluorescent tubulin. At 26 +/- 2 degrees C calmodulin exchanges rapidly with the relatively stable population of microtubules, suggesting that calmodulin is bound, either directly or indirectly, to microtubule walls.

Alkaloids↗

Neuronal and neuroglial responses following retinal lesions in the neonatal rats.

Lesions were produced in the nasal-superior quadrant of rat retinas at 1 day postnatal. Both the optic fiber and ganglion cell layers were destroyed at the lesion site. Retrograde changes in the more peripherally located ganglion cell bodies, their optic fibers, and neuroglia were monitored by light and electron microscopy. No optic fibers remained in the region peripheral to the lesion site after 2 days postoperative (DPO). Neither regenerative sprouting nor axonal ingrowth from late-maturing ganglion cells in the retinal periphery was observed. Cell death of the large and the majority of medium ganglion cell bodies was very rapid as was clearing of the degeneration products. These processes peaked at 1 DPO and were complete by 2 DPO. Microglia and Mueller cell cytoplasm actively phagocytized degenerating ganglion cell bodies and their optic fibers. A stable population of cell bodies in the ganglion cell layer peripheral to the lesion remained intact from 2 DOP to 21 DPO. The surviving somata were consistently 65% of the control ganglion cell population, and they remained after their axons had degenerated. The cell bodies measured 6-12.1 micron in diameter, a range which included the small cell population and a few of the medium cells. Dendritic patterning, used to designate ganglion cell types, corroborated their classification as small and medium ganglion cells. Morphological changes in these perikarya due to axotomy were limited to a mild chromatolytic response.

Animals↗

Effect of body position on maximal expiratory pressure and flow in adults with cystic fibrosis.

Maximum expiratory pressure (MEP) and peak expiratory flow rate (PEFR) are used as surrogate measures of cough and huff strength. Some body positions (particularly head-down tilt) significantly affect these measures in people with normal respiratory function and with chronic obstructive pulmonary disease. This may have implications for people with cystic fibrosis (CF), who use coughing and huffing and may use gravity-assisted drainage positions for airway clearance. Previous research concluded that body position does not affect MEP in people with CF, although head-down tilt was not examined and PEFR was not measured. This study investigated the effect of body position on MEP and PEFR in 20 adults with stable CF. Repeated measures of MEP and PEFR were performed across seven positions (standing, chair-sitting, sitting in bed with backrest vertical, sitting in bed with backrest at 45 degrees , supine, side-lying, and side-lying with head-down tilt 20 degrees ) in random order. During testing, reflux sensation and oxygenation were monitored. MEP was significantly reduced in side-lying and in the head-down tilt position. PEFRs were significantly reduced in the three-quarters sitting, supine, side-lying, and head-down positions. Oxygenation and reflux scores were worst in the head-down position. Despite statistical significance, the differences observed between positions in this stable population were of small magnitude. The effect of body position on MEP and PEFR may be more relevant during airway clearance treatments of the acutely unwell person with CF.

Adolescent↗

200 kD neurofilament protein and synapse elimination in the rat soleus muscle.

We studied the distribution and appearance of the phosphorylated form of the 200 kD neurofilament protein in the rat soleus muscle during the period of postnatal synapse elimination. Unlike many muscles, the appearance of singly innervated muscle cells in soleus occurs well after myogenesis has been completed, so that synapses are eliminated from a stable population of muscle cells. Immunoreactivity to the 200 kD neurofilament protein is present in the terminals of neuromuscular synapses of animals at all postnatal ages from 0 to 21 days. Before postnatal day 10, when physiological studies indicate that all soleus muscle cells receive more than one synaptic input, as many as 30% of soleus muscle cells contain phosphorylated 200 kD neurofilament protein immunoreactivity in only one synaptic terminal. At older ages the number of polyneuronally innervated muscle cells observed using immunostaining is similar to that observed physiologically. These findings suggest that not all developing neuromuscular synapses contain phosphorylated 200 kD neurofilament protein, and that those terminals lacking it comprise most of those eliminated early in the postnatal period. We conclude that the presence of phosphorylated 200 kD neurofilament protein might be highly correlated with the survival of motor nerve terminals during postnatal neuromuscular synapse elimination.

Animals↗

Taxol reduces the rate of cytokinesis in PtK1 cells.

Mitotic PtK1 cells were treated both during mid-anaphase and at furrow initiation with the potent microtubule (MT) stabilizing agent, taxol, to determine the role of MTs in the rate of cytokinetic events. Rates of cytokinesis (micron/min) were measured by changes in furrow diameter. Incubation of PtK1 cells during mid-anaphase with 5 micrograms/ml taxol slows the rate of cytokinesis by an average of 43%. Instead of furrow initiation to midbody formation taking an average of 10.7 min (1.6 microns/min), furrowing to midbody formation was completed in an average of 19.0 min (0.9 micron/min), which does not include the 7-min period between taxol application in mid-anaphase and furrow initiation. Application of 5 micrograms/ml taxol to cells at furrow initiation had a reduced effect on decreasing the rate of cytokinesis and midbody formation; furrowing to midbody formation took an average of 14.6 min (1.2 microns/min). These data suggest that delays in the rate of cytokinesis is dependent on the mitotic stage at which taxol is applied. Ultrastructural analysis shows that taxol treatment of anaphase cells prevents midbody formation during early G1, yet MT number and organization in the furrowed region is not significantly altered from untreated cells. There is little change in the organization and amount of contractile ring microfilaments, yet filaments are also found parallel to midbody MTs. Our results may be explained by the fact that taxol tends to stabilize MTs which probably affects the rate at which they depolymerize in the terminal phases of cytokinesis. Reduction in depolymerization rates of a stable population of MTs could serve to regulate the rate of cytokinesis.

Animals↗