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Biomedical subjects

C S Carter

Publications and source records attributed to C S Carter.

At least 145 records · Page 8Linked to original sources

Elevated serum lactate associated with panic attacks induced by hyperventilation.

Several lines of evidence suggest that lactate metabolism may be altered in panic disorder. We recently reported exaggerated increases in serum lactate in panic patients following hyperventilation during glucose infusion. In the current study, lactate metabolism was stimulated by hyperventilation following glucose ingestion in 12 panic patients and 12 controls. The seven patients who panicked during hyperventilation exhibited larger increases in serum lactate levels than nonpanicking patients or controls. The lactate response was significantly correlated with peak ratings of anxiety and panic symptoms, but not correlated with insulin or cortisol levels, heart rate, pCO2, adiposity, exercise habits, or diet. Hyperventilation-induced panic appears to be associated with metabolic changes leading to elevated serum lactate.

Adult↗

Central and peripheral effects of oxytocin administration in prairie voles (Microtus ochrogaster).

The present study examined the hypothesis that oxytocin (OT) may influence female sexual behavior in prairie voles (Microtus ochrogaster). The effectiveness of OT to induce sexual behavior was tested in ovariectomized females that were injected daily with estradiol benzoate (EB, 0.02 micrograms, twice), a dose insufficient for estrus induction. On the third day females received intracerebroventricular (ICV) injections of OT (1, 300, or 1000 ng) or saline vehicle. In the presence of minimal estrogen stimulation, OT did not induce sexual receptivity, or influence autogrooming or other social interactions. The behavioral effects of OT were examined in another group of ovariectomized females that received daily oil or EB injections (10 micrograms, twice) followed on the third day by either ICV (1, 300, or 1000 ng) or intraperitoneal (IP) (1, 3, or 10 micrograms) injections of OT. Among EB-treated females, only those in confirmed estrus, prior to ICV or IP injection, were included in these studies. There was a dose-related decrease in the percentage of females that remained in behavioral estrus after ICV OT. In those females that continued to show sexual behavior, lordosis frequencies and durations were unaffected by ICV OT. Nonsexual behavior did not differ between mated females and those exhibiting OT-inhibited sexual behavior. In females that were EB-treated, autogrooming and side-by-side behavior increased after ICV OT, while there was a decline in aggression. Female sexual and nonsexual behaviors were not significantly affected by IP OT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vivo traffic of indium-111-oxine labeled human lymphocytes collected by automated apheresis.

The in vivo traffic patterns of autologous lymphocytes were studied in five normal human volunteers using lymphocytes obtained by automated apheresis, separated on Ficoll-Hypaque gradients, and labeled ex vivo with 111In-oxine. Final lymphocyte infusions contained 1.8-3.1 X 10(9) cells and 270-390 microCi (9.99-14.43 MBq) 111In, or 11-17 microCi (0.41-0.63 MBq) per 10(8) lymphocytes. Gamma imaging showed transient lung uptake and significant retention of radioactivity in the liver and spleen. Progressive uptake of activity in normal, nonpalpable axillary and inguinal lymph nodes was seen from 24 to 96 hr. Accumulation of radioactivity also was demonstrated at the forearm skin test site, as well as in its associated epitrochlear and axillary lymph nodes, in a subject who had been tested for delayed hypersensitivity with tetanus toxoid. Indium-111-oxine labeled human lymphocytes may provide a useful tool for future studies of normal and abnormal lymphocyte traffic.

Blood Component Removal↗

In vivo distribution of adoptively transferred indium-111-labeled tumor infiltrating lymphocytes and peripheral blood lymphocytes in patients with metastatic melanoma.

Patients with metastatic melanoma undergoing therapy with cyclophosphamide (CPM), tumor-infiltrating lymphocytes (TIL), and interleukin-2 (IL-2) were studied for the ability of their 111In-labeled TIL or peripheral blood lymphocytes (PBL) to localize in sites of tumor using gamma camera imaging and biopsies. Nineteen infusions of radiolabeled TIL were given to 18 patients, while five patients received radiolabeled autologous PBL during TIL therapy. Clear tumor localization was seen on 13 of 18 nuclear scan series performed on 111In-TIL recipients, while tumor was imaged in only one of four scan sequences on patients given 111In-PBL. Nineteen paired biopsies of tumor and normal skin were completed on 10 patients receiving 111In-TIL, while eight biopsies were done on three PBL patients receiving 111In-PBL. The mean percentage of total injectate activity localizing per gram of tumor tissue was 0.0049% in the TIL group and 0.0010% in the PBL group (P2 = .0004). The mean of the tumor to normal skin ratios of the 111In-TIL group was three times that for 111In-PBL (P2 = .0072). One patient was studied by nuclear scanning on three consecutive treatment courses of CPM, TIL, and IL-2. He initially demonstrated clear tumor localization by 111In-TIL at several sites, then faint localization with 111In-PBL at a single site, and subsequently positive tumor imaging on repeat 111In-TIL infusion at multiple sites. These results confirm and expand our initial data demonstrating that human TIL transferred with CPM pretreatment and followed by IL-2 preferentially localize to tumor sites and indicate that this localization is greater for TIL than PBL.

Adult↗

Simulated drought influences reproduction in male prairie voles.

The environmental factors that arrest breeding in prairie voles during the middle of the breeding season are unknown. The role of water availability on reproductive function was examined by limiting water intake to 50% of ad lib water consumption for 10 weeks. At autopsy, testicular, epididymal and seminal vesicle masses were reduced in water restricted males as compared to animals with ad lib access to water. Body mass was also reduced in water restricted males. Plasma testosterone levels and the number of testicular and epididymal sperm were significantly reduced in water restricted voles as compared to animals drinking water ad lib, but plasma levels of luteinizing hormone were unaffected. Taken together, these data suggest that reduced water availability can inhibit male prairie vole breeding.

Animals↗

Hormonal correlates of sexual behavior and ovulation in male-induced and postpartum estrus in female prairie voles.

The purpose of the present study was a description of hormonal profiles in female prairie voles (Microtus ochrogaster) in estrus that was induced by male exposure versus postpartum estrus. Hormonal profiles are reported in sexually naive females and in sexually experienced females, as a function of varying amounts of coital stimulation and as a function of time since male exposure. Ovarian estradiol levels, uterine weights and uterine protein levels increased in virgin females after exposure to a male, were highest in females that showed lordosis, declined slowly when estrous females were isolated from males and decreased sharply following mating. Ovarian progesterone levels increased more rapidly following mating in females in male-induced estrus than in females in postpartum estrus. Serum progesterone levels did not increase significantly within 24 hr following mating, but were elevated by 72 hr after mating. These findings are discussed as they relate to the hormonal control of female sexual behavior.

Animals↗

Granulocyte transfusion therapy in a child with chronic granulomatous disease and multiple red cell alloantibodies.

A 7-year-old, 17-kg child with chronic granulomatous disease and nocardial pneumonia and osteomyelitis did not respond to antibiotic therapy and developed multiple red cell (RBC) alloantibodies (anti-c, -E, and -Jka). To provide daily granulocyte concentrates, a method was devised to reduce the number of incompatible RBCs per transfusion. Leukapheresis was done with hydroxyethyl starch, and the apheresis product was allowed to sediment by gravity in a plasma expressor for 90 minutes. The leukocyte-rich plasma was separated from the sedimented RBCs by transfer to a satellite bag, and the volume of the product was reduced by centrifugation to approximately 80 ml. RBC content was reduced from 29 +/- 7 to 2.5 +/- 1.0 ml (n = 22, p less than 0.01) and was accompanied by a 70 percent recovery of white cells (range, 49-90%). The final product contained 1.6 +/- 1.0 X 10(10) granulocytes. There were no clinical or laboratory signs of hemolysis during the course of 46 granulocyte transfusions, 37 of which were derived from c-, E-, or Jka-positive donors. The size of most apheresis donor pools is insufficient to provide phenotypically matched granulocyte concentrates daily for patients with RBC alloimmunization. The rapid, simple method described here may allow daily therapy with mismatched concentrates to be administered safely to such patients.

ABO Blood-Group System↗

Tumor localization of adoptively transferred indium-111 labeled tumor infiltrating lymphocytes in patients with metastatic melanoma.

Lymphoid cells infiltrating into human tumors can be expanded in vitro in medium containing interleukin-2 (IL-2). Adoptive transfer of these tumor-infiltrating lymphocytes (TIL) mediates potent antitumor effects in murine tumor models. Clinical trials to evaluate the efficacy of these cells in patients with advanced cancer are underway. We have investigated whether infused TIL labeled with indium 111 (111In) oxine can traffic and localize to metastatic deposits of tumor. Six patients with metastatic malignant melanoma who had multiple sites of subcutaneous, nodal, and/or visceral disease were the subjects of the study. The patients received cyclophosphamide 36 hours before receiving the intravenous (IV) infusion of TIL followed by IL-2 IV every eight hours. The distribution and localization of the TIL were evaluated using serial whole body gamma camera imaging, serial blood and urine samplings, and serial biopsies of tumor and normal tissue. 111In-labeled TIL localized to lung, liver, and spleen within two hours after the infusion of activity. Activity in the lung diminished within 24 hours. As early as 24 hours after injection of 111In-labeled TIL, localization of TIL to sites of metastatic deposits was demonstrated in all six patients using either imaging studies or biopsy specimens or both. 111In activity in tumor tissue biopsies ranged from three to 40 times greater than activity in normal tissue. A progressive increase in the radioactive counts at sites of tumor deposit was seen. This study shows that labeled TIL can localize preferentially to tumor, and provides information concerning the possible mechanism of the therapeutic effects of TIL.

Adult↗

A simplified automated procedure for generation of human lymphokine-activated killer cells for use in clinical trials.

The administration of lymphokine-activated killer (LAK) cells along with interleukin-2 (IL-2) can mediate regression of tumors in selected patients. A closed automated system utilizing commercial blood cell separators has been developed for washing and Ficoll-Hypaque (FH) separation of lymphocytes, for lymphocyte culture in polyolefin bags, and for concentration of LAK cells out of culture prior to infusion. We now demonstrate that preparation of LAK cells can be simplified by elimination of the FH sedimentation step. Patient leukapheresis was performed using Fenwal CS-3000 blood cell separators, with a mean cellular yield per procedure of 54 X 10(9) WBC (95% lymphocytes), 184 X 10(9) RBC, and 306 X 10(9) platelets (n = 22). These cells were then washed in the same apheresis kit with a counter-current flow of saline, thereby eliminating 85% of platelets while retaining 88% of WBC. Aliquots of the washed cells were separated on FH gradients in 50 ml centrifuge tubes, and both FH-separated and washed-only cells were cultured at 3 X 10(6)/ml with 1500 U/ml IL-2 in polyolefin bags. Cytotoxicities of 22 preparations of LAK cells from 14 patients were evaluated in 4 h 51Cr release assays. Cells that were washed-only averaged 47, 35, and 9 lytic units/10(6) cells against K562, Daudi, and fresh tumor, while FH separated cells averaged 46, 33, and 6 lytic units/10(6) cells respectively. Cellular recoveries using the wash-only technique were 25% greater than when using FH sedimentation. Omission of FH separation saves time and expense in preparation and provides greater numbers of LAK cells for use in adoptive immunotherapy.

Autoanalysis↗

Technical aspects of lymphokine-activated killer cell production.

Adoptive immunotherapy is a novel approach to treating patients with cancer, utilizing as therapy a patient's own peripheral blood lymphocytes that have been activated by incubation with interleukin-2 (IL-2). These cells develop the ability to mediate tumor regression in vivo and are referred to as lymphokine-activated killer (LAK) cells. The production of LAK cells is a complex and labor-intensive process. Lymphocytes are collected by continuous-flow centrifugation, purified on Ficoll-Hypaque (FH) density gradients, incubated in vitro with IL-2, and then harvested for infusion into the patient. An automated approach to LAK cell generation has been developed using the Fenwal CS-3000 cell separator and polyolefin PL-732 blood storage bags. Lymphocyte concentrates (LC) containing 6.5 x 10(9) mononuclear cells per pack were obtained using standard leukapheresis techniques. Disposable apheresis kits were then modified to allow the LC to be pumped into the separation chamber along with a counter-centrifugal flow of saline, removing the platelets and plasma by elutriation. The remaining cells were underlaid with FH, displacing the lymphocytes into a collection bag, where they were washed and concentrated. Mean leukocyte recovery was 59.2% (99.9% lymphocytes, n = 14). The final product contained 6.7% of the initial platelets and had a hematocrit of less than 1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Automation↗

Effects of hormonal, sexual, and social history on mating and pair bonding in prairie voles.

The interactive effects of hormones, sexual history and cohabitation on sexual and social behaviors were examined in pairs of ovariectomized female and sexually experienced male prairie voles (Microtus ochrogaster). Monitoring with time lapse video tape revealed that females in estradiol benzoate (EB)-induced estrus, and their male partners engaged in high levels of sexual activity which continued intermittently for at least 3 days (until observations were arbitrarily terminated). In conjunction with other studies, these results indicate that the hormonal condition of the female at the time of testing is a major determinant of sexual activity. Prior hormonal, copulatory, or cohabitation experience did not significantly influence sexual responses between females and unfamiliar male partners. However, affiliative behaviors, such as side by side contact, were higher in pairs that were familiar due to prior sexual and cohabitational experience. These results indicate that social and sexual behaviors are independently regulated. Other behaviors, including nasogenital investigation and autogrooming were influenced by the hormonal and sexual history of the female. The implications of these behavioral patterns for reproductive activation, pair bonding, and incest avoidance are discussed.

Animals↗

Males increase progestin receptor binding in brain of female voles.

In female prairie voles, behavioral estrus is induced by exposure to an unfamiliar male and ovulation is induced by mating. Experiments were conducted to determine whether a saturable high-affinity progestin binding site (PRC) is present in cytosols of brain tissue from females exposed to male stimuli for a period of time which is sufficient to bring most females into heat. PRC were detected in both the medialbasal hypothalamus (MBH) and preoptic area (POA). However, PRC levels increased in response to male stimuli in the MBH but not in the POA. The lack of an increase in the POA could not be attributed to changes in circulating progesterone. These results indicate that social stimuli can influence cellular events within specific areas of the female brain and suggest that one distinguishing feature between the spontaneous and induced ovulators may be the pattern of estrogen-induced progestin receptors within areas of the brain which are involved with the control of sexual behavior and/or ovulation.

Animals↗

Development of an automated closed system for generation of human lymphokine-activated killer (LAK) cells for use in adoptive immunotherapy.

Immunotherapy utilizing the adoptive transfer of lymphokine-activated killer (LAK) cells in conjunction with recombinant interleukin-2 (IL-2) can mediate tumor regression in some patients with advanced cancer. The activation of large numbers of LAK cells was performed in roller bottles in a research laboratory setting and required meticulous aseptic technique, at least one skilled technician per patient and one laminar flow hood per patient. To reduce the complexity and expense of LAK cell generation for human immunotherapy trials we have developed a closed-system automated procedure using a continuous flow blood cell separator. PBL were obtained by standard apheresis techniques. Platelets and plasma were elutriated using countercentrifugal flow of saline in the cell separator machine. The washed PBL were underlaid with Ficoll-Hypaque (FH) in the original separation bag. Lymphocytes were then flushed into a collection bag where they were concentrated and washed with 2 liters of saline. Mean recovery from the automated FH technique was 54.6 +/- 4.3% compared to 62.3 +/- 4.0% using manual methods in 50 ml tubes (P greater than 0.05). Cells were diluted in the collection bag with RPMI 1640 +/- 2% human AB serum and could be dispensed in an automated fashion to polyolefin bags via a sample port with 1000-1500 U/ml IL-2. After 3-4 days of culture in 5% CO2 at 37 degrees C, activated cells from the bags were harvested and washed in a closed system using the continuous flow cell separator. Cell yield from the harvest was 79.2 +/- 5.4% in the automated system compared to 64.9 +/- 5.0% in the standard procedure using manual harvest of roller bottles (P less than 0.01). Lytic capacity of the cells against fresh human tumor in a 4 h 51Cr release assay was equivalent in cells processed either by the automated or the conventional manual method. The advantages of a closed system include decreased potential for microbial contamination and reduced labor and capital equipment costs. This technique may be easily adapted for use with other cell collection and culture systems.

Cell Separation↗

Estrogen and the induction of lordosis in female and male prairie voles (Microtus ochrogaster).

Estrogen elicited lordosis in ovariectomized female prairie voles (Microtus ochrogaster). Treatment with estradiol benzoate (EB) was particularly effective if administered as multiple injections. Very high dose levels were not, in general, any more effective than lower doses. Individual animals typically showed lordosis within 24 to 48 hr following the onset of EB treatment and prolonged treatments did not increase the percentage of females responding to EB. Castrated male prairie voles did not respond with lordosis to repeated daily injections of 10 micrograms EB given for a period of 15 consecutive days.

Animals↗

Male stimuli are necessary for female sexual behavior and uterine growth in prairie voles (Microtus ochrogaster).

In reproductively naive female prairie voles (Microtus ochrogaster) direct contact with male urine or housing in a male-soiled cage, in the absence of physical contact, resulted in increased uterine weights, but did not reliably elicit behavioral estrus (defined by lordosis). Physical contact with an unfamiliar male, for 1 hr or more, followed by 30 or 48 hr of continuous access to a male-soiled cage, induced lordosis in approximately two-thirds of the females tested. When females were physically exposed to a male for 18 hr and tested 6 hr later, 70% showed lordosis. However, when females receiving either 1 or 18 hr of male contact were removed from the presence of the male and placed in a clean cage for 24 hr, only 29-37% of the females subsequently showed lordosis. These results suggest that direct physical contact with the male or chemical stimuli from the male may be necessary to induce and maintain behavioral estrus in female prairie voles.

Animals↗

Males increase serum estrogen and estrogen receptor binding in brain of female voles.

Sexual development of female prairie voles does not occur unless females are exposed to stimuli from an unfamiliar male. Three experiments were conducted to determine whether a saturable high-affinity estradiol binding site (ERN) is present in cell nuclei of brain tissue from females exposed to male stimuli and whether serum estradiol and brain ERN are correlated with the duration of male exposure. Brain ERN were detected and found to be correlated with serum estradiol levels. Significant increases in brain ERN were observed within 18 hours after females were exposed to a male for either a continuous (uninterrupted) or transient (1 1/4 hour) period. A significant increase in serum estradiol was observed for females given continuous male exposure. The rate of increase of ERN in brain was significantly higher for females given continuous as opposed to transient male exposure. The results suggest that the continued presence of a male can accelerate the rate of increase of ERN in the brain, presumably through increases in circulating estradiol.

Animals↗

Optimization of parameters for maximization of plateletpheresis and lymphocytapheresis yields on the Haemonetics Model V50.

Automated apheresis techniques afford the opportunity of tailoring collection parameters for each donor's hematologic profile. This study investigated the effect of various settings of the volume offset parameter as utilized in the Haemonetics Model V50 instrumentation during platelet- and lymphocytapheresis to optimize product yield, purity, and collection efficiency. In both types of procedures, increased product yield could be obtained by using an increased volume offset for donors having lower hematocrits. This improvement was related to an increase in collection efficiency. Platelet products also contained fewer contaminating lymphocytes with this approach. Adjustment of the volume offset parameter can be utilized to make the most efficient use of donors and provide higher-quality products.

Automation↗

Social isolation inhibits male-like sexual behavior in female hamsters.

In the female golden hamster, Mesocricetus auratus, group housing permits the expression of male-like behavioral patterns including mounting and pelvic thrusting toward an estrous stimulus female. Sixty percent of females housed in groups of five showed these behaviors, while singly housed females were rarely observed to show mounting or thrusting. Females weaned at 19 or 35 days of age did not differ in their tendencies to show male-like behavioral patterns. Virtually all observations of mounting and pelvic thrusting behaviors were made on days when the females being tested were in behavioral estrus. These findings differ from previous studies which have reported that masculine behavioral patterns are rare in normal female hamsters. In previous studies females that were evaluated were typically not in behavioral estrus and were not housed for long periods of time with other intact females. Social factors interact with hormonal state to contribute to the expression of male-like behaviors in female hamsters.

Animals↗