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C W Jackson

Publications and source records attributed to C W Jackson.

At least 55 records · Page 3Linked to original sources
PubMed1995

A flow cytometric assay using mepacrine for study of uptake and release of platelet dense granule contents.

Diagnosis of platelet dense granule storage pool disease and release defects at present requires a combination of studies including lumiaggregometry, conventional platelet aggregation, radioactive serotonin uptake and release, and electron microscopy. Flow cytometric methods have been developed to study platelet activation, aggregation, and alpha-granule protein release. Here, we have investigated the use of flow cytometry for analysis of platelet dense granule content uptake and release using mepacrine as a fluorescent marker. Mepacrine (quinacrine) is rapidly taken up and localized in dense granules of platelets. For the assay, as little as 20 microliters of blood from a fingerstick collected without anticoagulant or venous blood collected in 3.8% sodium citrate were diluted 1:40 with 2 ml Hanks balanced salt solution (BSS). 300 microliters of this cell suspension were incubated with mepacrine alone, or simultaneously with a mouse monoclonal antibody to human platelet glycoprotein IIb (Tab), used as a platelet-specific marker. The bound monoclonal antibody was then indirectly labelled with the fluorochrome, RED670. 100 microliters of the sample were further diluted with Hanks BSS for one- or two-colour flow cytometric analysis. To verify that mepacrine uptake was related to platelet dense granule content, platelets of beige mice, a strain with dense granule deficiency, were examined. Their mepacrine uptake was substantially decreased compared to that of normal mice. Decreased mepacrine uptake also was demonstrated in platelets of a patient with Hermansky-Pudlak syndrome in which a deficiency of platelet dense granules is characteristic. In both human and mouse platelets, mepacrine uptake was proportional to platelet size. Thrombin induced mepacrine release in a dose-dependent manner from 0.003 to 0.4 U/ml. Therefore both platelet uptake and release of mepacrine can be readily detected by flow cytometry. Flow cytometry provides an attractive alternative to aggregation and radioactive serotonin as methods to study defects in platelet dense granule function.

Animals↗
PubMed1995

Obsessive-compulsive disorder in elderly patients.

Obsessive-compulsive disorder (OCD) is a common illness which starts in young adulthood and persists into late life. OCD is associated with dysregulation of the serotonin system and may also be related to the dysregulation of dopamine. When OCD starts in an elderly patient, either an organic or a neurological diagnosis should be considered. Clomipramine and serotonin reuptake inhibitors are the mainstay of treatment for OCD. Choice of a particular agent should be based on the patient's previous response and the adverse effect profile of the drug. Pharmacokinetics should also be a consideration due to age-related changes in hepatic and renal function leading to increased plasma concentrations as well as prolonged elimination half-lives of these agents. Behavioural therapy, in addition to pharmacological management, is essential to treat compulsions and to improve response.

Aged↗
PubMed1995

Delirium associated with clozapine and benzodiazepine combinations.

Delirium has many organic causes, one of which is the combination of medications. This is sometimes difficult to differentiate in the psychotic individual. To our knowledge there are no published cases of delirium definitively established by "rechallenge" with a combination of clozapine and benzodiazepines. Lorazepam was given for agitation in two individuals on clozapine. Because of either the short half-life, or the lack of knowledge about this interaction, multiple doses were given. Clonazepam was given to a third individual. Two of the reported individuals developed a delirium associated with the administration and onset of lorazepam. These patients had received both lorazepam and clozapine singularly in the past without the adverse effects seen with the combination. Both patients were rechallenged with second doses of lorazepam, when they again developed a delirium. In one case the patient was admitted on clonazepam and then started on clozapine. A delirium developed at a clozapine dose of 150 mg/day; she was not rechallenged. In all three cases the patients' sensorium cleared when benzodiazepines were discontinued. The combination of benzodiazepines and clozapine should be avoided if possible, and if they are used in combination, it should be with great caution.

Adult↗
PubMed1995

Efficacy and adverse effects of clozapine in four elderly psychotic patients.

BACKGROUND: Clozapine is an atypical antipsychotic agent that is effective in refractory schizophrenic patients. Older patients may have various psychotic manifestations that may not be responsive to typical neuroleptic therapy. There may also be patient-specific factors--declines in reserve capacity and homeostasis, and age-related changes in the pharmacokinetics and pharmacodynamics of drugs--in older patients that increase their susceptibility to the side effects of psychotropic medications. While clozapine has few extrapyramidal side effects, it has other side effects that may be problematic in the older population. METHOD: In our geropsychiatric unit, clozapine was prescribed for four patients over the age of 65 years. All patients were either experiencing psychotic symptoms refractory to other antipsychotic medications or had relative contraindications to a typical neuroleptic. Two of the four were chronic schizophrenics, and three of the four also presented with dementia. RESULTS: Two of the four patients did eventually receive relief of psychotic symptoms from clozapine. All four experienced events after initiation of clozapine therapy, which included falls (2 patients), symptomatic bradycardia (2 patients), and delirium (1 patient). All these adverse effects occurred on doses ranging from 6.25 to 37.50 mg/day, and the three patients with moderate-to-severe dementia experienced these severe adverse effects after administration of the first dose. CONCLUSION: Clozapine may be a useful drug for older patients with psychotic symptoms; however, at current dosage recommendations, adverse events may occur, especially on first dose. Well-designed studies need to be performed to assess the effectiveness and dosage ranges for this population.

Accidental Falls↗
PubMed1995

Castration decreases thrombocytopoiesis and testosterone restores platelet production in castrated BALB/c mice: evidence that testosterone acts on a bipotential hematopoietic precursor cell.

BALB/c male mice have higher platelet counts than female mice of the same strain. To test the hypothesis that testosterone influences platelet production, we evaluated indices of both red blood cell and platelet production in intact male BALB/c mice, in male mice 4 weeks after castration, and in castrated mice administered maintenance doses of testosterone as testosterone propionate. As predicted, castration resulted in decreased hematocrit and body weight in BALB/c mice. Body weights and hematocrits returned to noncastrated levels after 2 and 7 days, respectively, of administration of testosterone. Total circulating red blood cell mass and total circulating red blood cell count were both decreased by castration and were returned to control (noncastrated) levels after 2 days of testosterone therapy. Reticulocyte counts were not changed by castration, but they increased above counts of uncastrated and castrated control mice after 3 days of testosterone administration. White blood cell (WBC) numbers were unaffected by castration or testosterone administration. Additionally, platelet count (956 vs 834 x 10(3)/microliters), platelet size (3.87 vs 3.75 microns3), sulfur 35 incorporation into platelets (6.36 vs 4.87 x 10(-3)%), mean megakaryocyte ploidy (17.43N vs 16.89N), total circulating platelet mass (TCPM) (490 vs 379 x 10(8) microns3), and total circulating platelet count (TCPC) (131 vs 103 x 10(7)) were significantly (p < 0.05) decreased in castrated mice as compared with intact control mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Mode of inheritance of the higher degree of megakaryocyte polyploidization in C3H mice. I. Evidence for a role of genomic imprinting in megakaryocyte polyploidy determination.

C3H mice have higher average ploidy megakaryocytes than all other mouse strains tested, but the mode of inheritance of this anomaly is unknown. Therefore, to clarify the genetics of high ploidy megakaryocytes in C3H mice, we measured megakaryocyte DNA content from both male and female offspring from F1, as well as backcross matings. In all, offspring from seven different matings of mice were studied: (1) C57BL X C57BL (the first strain listed is the male parent in each case), (2) B6C3F1 (offspring from C57BL X C3H mating) X C57BL, (3) C57BL X B6C3F1, (4) C57BL X C3H, (5) C3H X B6C3F1, (6) B6C3F1 X C3H, and (7) C3H X C3H. The polyploid megakaryocyte DNA content distributions of the offspring from these matings show that C3H mice have higher percentages of high ploidy megakaryocytes than did all other mice. Also, male mice had significantly higher percentages of high ploidy (32N and 64N) megakaryocytes than did female mice for all matings, except backcross mating no. 6. The megakaryocyte DNA content for individual offspring of a given backcross appeared to form a single, continuous distribution, rather than segregate into two distinct groups, suggesting that the higher megakaryocyte DNA content of C3H mice is caused by involvement of multiple allelles. This conclusion is further supported by our finding that the frequency of high ploidy megakaryocytes among offspring of the various matings was related to the proportion of C3H genotype contributed by the parents, ie, average megakaryocyte DNA content increased linearly (r2 = .88 for male mice and .84 for female mice. P < .0001) with increasing C3H gene dosage; the correlations for both male and female mice were essentially parallel (slope = 0.08 and 0.09, respectively). In addition, we found an effect of genomic imprinting on megakaryocyte DNA content in backcross offspring. The genetic imprinting was characterized by the female parent having a greater influence on the offspring's megakaryocyte DNA content than the male parent, ie, although the overall genetic makeup was the same, female offspring from backcross no. 6 (in which the female was C3H) had higher average megakaryocyte ploidy values than those from backcross no. 5 (in which the female was B6C3F1).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Pharmacologic management of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is an intriguing, difficult problem characterized by anxiety-producing intrusive thoughts and performance of anxiety-reducing rituals. Current evidence suggests that OCD may be associated with dysregulation of serotonin and dopamine neurotransmission. Numerous early studies involving the serotonin-specific reuptake inhibitor clomipramine led to the formulation of this hypothesis. Positive results with clomipramine initiated further research with other serotonin-specific reuptake inhibitors, such as fluoxetine, fluvoxamine, sertraline, and serotonergic agents such as buspirone and trazodone. Findings from a number of clinical trials suggest that drugs that inhibit serotonin reuptake or affect serotonergic transmission in other ways are of clear benefit in the treatment of OCD. These drugs may be more effective for obsessive thoughts than for compulsive rituals. Effective pharmacotherapy can dramatically decrease obsessive-compulsive symptoms and improve the patient's quality of life.

1-Naphthylamine↗
PubMed1994

Prophylaxis of carbamazepine-induced hyponatremia by demeclocycline in six patients.

BACKGROUND: Hyponatremia has been reported to occur in approximately 5% of carbamazepine-treated patients who otherwise do well on that agent. Demeclocycline has been used in the treatment of hyponatremia of various etiologies including one case of carbamazepine-induced hyponatremia. METHOD: We extended these observations by studying the effects of demeclocycline on carbamazepine-induced hyponatremia in six psychiatric inpatients. RESULTS: Once serum sodium concentrations had normalized after carbamazepine discontinuation, demeclocycline prevented further decreases in sodium levels upon rechallenge with carbamazepine in five of six patients. Gender, smoking, and neurologic compromise may have played a role in the development of carbamazepine-induced hyponatremia as well as response to this strategy, although our sample size is too small to make firm conclusions. CONCLUSION: Demeclocycline was successfully used in the prophylaxis of carbamazepine-induced hyponatremia and may be useful in cases that respond best to carbamazepine treatment.

Adult↗
PubMed1994

The role of genotype, genomic imprinting, and sex hormones in platelet and megakaryocyte production.

Our previous data suggested that the higher average ploidy of C3H mouse megakaryocytes is the result of interaction of multiple alleles that act in an additive fashion. Average megakaryocyte DNA content increased with the proportion of C3H genotype. Other factors also influence megakaryocyte ploidy; male mice had megakaryocytes of higher ploidy than did female mice, and the genes that determine megakaryocyte ploidy had a differential expression, depending on the sex of the parent, a finding that suggests genomic imprinting. The role of genotype (and, thus, megakaryocyte DNA content) on other parameters of platelet production and megakaryocytopoiesis has not been examined. Therefore, we report the effects of genotype on platelet counts, platelet sizes, percent 35S incorporation into platelets, total circulating platelet counts (TCPC), total circulating platelet masses (TCPM), megakaryocyte size and number, and total megakaryocyte masses (TMM). Platelet counts of male mice were inversely related to the proportion of C3H genotype. In other words, male mice with a higher proportion of C3H genotype had lower platelet counts than did male mice with predominantly C57BL genotype (p = 0.04). None of the other platelet production indices were significantly correlated with the C3H genotype content of the offspring. However, a significantly positive correlation (p < 0.0001 for males and p < 0.003 for females) was found between megakaryocyte size and megakaryocyte ploidy. Although no significant difference in megakaryocyte numbers was noted, TMM of male mice was positively correlated (p < 0.05) with megakaryocyte ploidy. Male mice had higher platelet counts, percent 35S incorporation into platelet values, TCPC, and TCPM than did female mice, but platelet sizes were the same for both sexes. Megakaryocyte sizes, numbers, and TMM were higher in male than female offspring of some matings, but in several cases, sex did not appear to affect these parameters. Previous work has shown that this difference in platelet production capabilities due to sex of the mouse is most likely caused by male sex hormones. Evidence of different genetic expression (genomic imprinting), depending on the sex of the parent, was found in platelet counts and TCPC of certain backcrosses of female mice and in platelet sizes of male mice (p < 0.05). Therefore, we show that genotype, male sex hormones, and genomic imprinting influence platelet production in mice, but platelet counts of male mice were negatively correlated with size and DNA content of megakaryocytes.

Animals↗
PubMed1992

A unique talin antigenic determinant and anomalous megakaryocyte talin distribution associated with abnormal platelet formation in the Wistar Furth rat.

Rats of the Wistar Furth (WF) strain have hereditary macrothrombocytopenia with decreased platelet alpha-granule proteins. The autosomal recessive pattern of inheritance of the large mean platelet volume (MPV) phenotype and platelet alpha-granule protein deficiencies suggest that a component common to both formation of platelet alpha-granules and subdivision of megakaryocyte cytoplasm into platelets is quantitatively or qualitatively abnormal in WF megakaryocytes and platelets. We examined WF platelets for such an abnormality using electrophoretic and immunologic analyses. Rabbit antiserum prepared against WF rat platelets and absorbed with Wistar rat platelets recognized a major 235-Kd band, and minor bands of WF rat platelets ranging from 200 to 130 Kd, not present in immunoblots of Wistar, Sprague-Dawley, or Long-Evans rat platelets. The minor bands were labeled with affinity-isolated antibody to the 235-Kd band, indicating that all bands contained the same unique antigenic site. The 235-Kd antigen had the same mobility as rat platelet talin identified with a platelet antitalin antibody. Activation of calcium-dependent proteases during Triton X-100 extraction caused conversion of the 235-Kd antigen into a major fragment of 200 Kd and minor fragments ranging to 115 Kd, identical in mobility to fragments of rat platelet talin produced in the same samples. The absorbed anti-WF platelet antiserum also detected a 235-Kd antigen in WF lung, kidney, and small intestine by immunoblotting. Finally, the 235-Kd antigen unique to WF rats was immunoprecipitated from Triton X-100 supernatants of WF platelets with an antitalin monoclonal antibody (MoAb). These data indicate that the unique antigenic site is on WF talin. Examination of talin distribution in Wistar megakaryocytes showed localization beneath the plasma membrane, on the cytosolic face of demarcation membranes, associated with alpha-granule membranes, and diffusely throughout the cytoplasm. Although WF megakaryocytes showed the same general distribution pattern, some differences were apparent. In contrast to membrane systems of the Wistar rat, the large membrane complexes in WF megakaryocytes contained little or no talin. In addition, approximately half of WF megakaryocytes showed an increased peripheral localization of talin, often associated with membrane blebs, with decreased talin in the cytoplasmic interior. The association of the unique talin antigenic determinant and anomalous megakaryocyte talin distribution with abnormal platelet formation in WF rats suggests that talin is abnormal in this rat strain and that talin plays an important role in subdivision of megakaryocyte cytoplasm into platelets.

Animals↗
PubMed1992

Megakaryocytopoiesis and platelet production are stimulated during late pregnancy and early postpartum in the rat.

Platelet count during uncomplicated pregnancy shows considerable patient variation. To gain a better understanding of thrombocytopoiesis during pregnancy, megakaryocytes and platelets were examined during gestation and the early postpartum period, using as a model the rat. Platelet counts and megakaryocyte concentrations and DNA content distributions of timed-pregnant rats were examined at intervals from day 10 of gestation through parturition on day 22 and days 1 through 7 postpartum. Platelet survival was studied in late gestation and the early postpartum. Platelet volume was measured on gestation day 21. Platelet counts were moderately increased on gestation days 17 and 19 through 22, and on days 2 to 3 postpartum. However, the actual rate of platelet production was much higher than the platelet count suggests because the blood volume increased in late gestation to 1.5 times the nonpregnant level. Mean platelet volume and platelet volume distribution width of day 21 gestation rats were not significantly altered. Platelet survival in pregnant rats was not significantly different from that in nonpregnant females. In contrast, megakaryocyte concentration was significantly increased on gestation days 12, 17, and 19 through 21, and 2 to 3 days postpartum. In addition, in late gestation, megakaryocyte DNA content distributions displayed a marked increase in the proportion of high ploidy cells, which peaked 1 day before parturition. At that time, the proportions of 32N (43%) and 64N cells (3%) were, respectively, three and four times nonpregnant values. In contrast to megakaryocyte concentration, megakaryocyte DNA content distributions had returned to the nonpregnant pattern by day 1 postpartum. The changes in megakaryocyte DNA content distribution were accompanied by changes in megakaryocyte size. These data indicate that thrombopoiesis is substantially increased during late pregnancy, and that this increase is accomplished through an increase in megakaryocyte DNA content and size, as well as megakaryocyte number. The more rapid return of megakaryocyte DNA content than of megakaryocyte concentration to nonpregnant levels postpartum suggests that pregnancy-associated hormonal changes which produce an increase in megakaryocyte DNA content and size differ from those which cause an increase in megakaryocyte number.

Animals↗
PubMed1992

Rheologic properties of senescent erythrocytes: loss of surface area and volume with red blood cell age.

The rheologic properties of senescent erythrocytes have been examined using two models of red blood cell (RBC) aging. In the rabbit, aged erythrocytes were isolated after biotinylation, in vivo aging, and subsequent recovery on an avidin support. Aged RBCs from the mouse were obtained using the Ganzoni hypertransfusion model that suppresses erythropoiesis for prolonged periods of time allowing preexisting cells to age in vivo. In both cases, the aged erythrocytes were found by ektacytometry to have decreased deformability due to diminished surface area and cellular dehydration. The aged rabbit erythrocytes were further characterized by micropipette methods that documented an average surface area decrease of 10.5% and a volume decrease of 8.4% for the cells that were 50 days old. Because both the surface area and volume decreased with cell age, there was little change in surface-to-volume ratio (sphericity) during aging. The aged cells were found to have normal membrane elasticity. In addition, human RBCs were fractionated over Stractan density gradients and the most dense cells were found to have rheologic properties similar to those reported for the aged RBCs from rabbits and mice, although the absolute magnitude of the changes in surface area and volume were considerably greater for the human cells. Thus, stringent density fractionation protocols that result in isolation of the most dense 1% of cells can produce a population of human cells with rheologic properties similar to senescent cells obtained in other species. The data indicate that progressive loss of cell area and cell dehydration are characteristic features of cell aging.

Animals↗
PubMed1992

Effects of hypoxia on megakaryocyte size and number of C3H and BALB/c mice.

In an effort to explain the different platelet production capabilities of both normal and hypoxic male and female C3H and BALB/c mice, megakaryocyte size and number were determined utilizing bone marrow from both normal and hypoxic mice. The results indicate that normal BALB/c female mice have increased numbers of megakaryocytes, but of smaller size compared with either BALB/c male mice or to both sexes of C3H mice. An inverse relationship between the size and number of megakaryocytes was found in both normal and hypoxic mice; therefore, to evaluate total megakaryocyte characteristics, we calculated total megakaryocyte masses (TMM). With hypoxia, megakaryocyte number decreased, whereas megakaryocyte size increased. Despite the increase in megakaryocyte size, hypoxia caused a significant decrease in TMM (P less than 0.005) in all mice, but female C3H mice had higher TMM (P less than 0.05) than did female BALB/c mice. These data show that hypoxia decreases TMM in mice, and that the effect is greater in C3H mice than in BALB/c mice.

Animals↗
PubMed1992

Comparison of platelet production in two strains of mice with different modal megakaryocyte DNA ploidies after exposure to hypoxia.

Thrombocytopenia develops with prolonged exposure to hypoxia. Although decreases in megakaryocyte numbers due to hypoxia have been well documented, the effects of hypoxia on megakaryocyte DNA content have not been reported. In this study, megakaryocytopoiesis and platelet production were compared in both C3H mice (whose megakaryocyte modal ploidy class is 32N) and C57/BL mice (whose modal ploidy class is 16N), by enclosure in cages covered with silicone-rubber membranes. After equilibration, O2 levels inside the cages were 6%-7%. Hematocrits, platelet counts, platelet sizes, percent 35S incorporation into platelets, megakaryocyte size and number, and megakaryocyte DNA content of mice were measured before and at various days after hypoxia. Although hematocritis increased and platelet counts decreased in both strains of mice with time in hypoxic chambers, megakaryocyte and platelet responses of C3H mice differed from those of C57/BL mice in several respects; hematocrits of C3H mice were higher and platelet counts were lower than those in C57/BL mice. C3H mice produced larger platelets than C57/BL mice in response to hypoxia. Total circulating platelet counts (TCPC) and total circulating platelet masses (TCPM) of both mouse strains showed similar biphasic responses, that is, elevated TCPC and TCPM on days 2-4 and decreased values after 6-14 days of hypoxia. However, hypoxic C3H mice had lower TCPC on days 4-14 and lower TCPM on days 10-14 of hypoxia than C57/BL mice. Both C3H and C57/BL mice had decreased megakaryocyte numbers at 6-10 days of hypoxia, but only C3H mice had decreased numbers of megakaryocytes at day 14. Elevated megakaryocyte size was observed in both mouse strains at day 14 of hypoxia. However, after hypoxia, C3H mice showed a greater depression in megakaryocyte number and a larger increase in megakaryocyte sizes than did C57/BL mice. C3H mice maintained 32N as the modal megakaryocyte DNA content through day 10 of hypoxia, but 64N was the modal megakaryocyte DNA content at day 14; 16N remained the modal megakaryocyte DNA content in hypoxic C57/BL mice. Hypoxic C3H mice had an increase in 16N megakaryocytes after 6 days of hypoxia, followed by an increase in the proportion of 64N cells at 14 days compared to values of untreated C3H control mice. Hypoxic C57/BL mice had an increased proportion of 16N cells at 6 days but a decreased proportion of 32N cells at 14 days. These studies demonstrate that the decreased platelet production resulting from prolonged exposure to hypoxia is primarily the result of decreased differentiation of hematopoietic precursors into the megakaryocyte lineage rather than decreased megakaryocyte DNA content, because higher ploidy classes actually increase as thrombocytopenia becomes more severe. Stem cell competition could explain the findings of reduced platelet production and increased red blood cell production in both strains of mice after exposure to hypoxia.

Animals↗