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Biomedical subjects

T M Lee

Publications and source records attributed to T M Lee.

At least 127 records · Page 7Linked to original sources

Testosterone influences hibernation in golden-mantled ground squirrels.

At different phases of the hibernation season, castrated male golden-mantled ground squirrels were implanted with capsules that either were filled with testosterone (T) or left empty (blank). Blank-treated animals hibernated normally when housed at 5 degrees C. Entry into hibernation was prevented in the majority of squirrels treated with T several days before the initial cold challenge. T concentrations that inhibited torpor (greater than 1.2 ng/ml) were comparable with those of intact males at the end of the hibernation season. In some squirrels, moderate T concentrations were compatible with hibernation, but torpor bout duration was shorter than normal. The inhibitory effect of T on hibernation did not appear to require aromatization of T to estradiol. We suggest that a steroid-independent mechanism triggers arousal from hibernation and that T-dependent processes determine whether hibernation is resumed at the end of an arousal period.

Animals↗

Temperature dependence of circadian rhythms in golden-mantled ground squirrels.

We tested the hypothesis that the free-running period and phase angles of entrainment of circadian locomotor activity rhythms of golden-mantled ground squirrels (Spermophilus lateralis) vary as a function of body temperature (Tb). Animals were maintained in a light-dark cycle (LD 14:10), and at 6-week intervals ambient temperature (Ta) was changed from 20 degrees to 30 degrees C, or vice versa. Data were collected during the animals' homeothermic and heterothermic phases. Subsequently, squirrels were housed in dim constant illumination with the same alternating temperature sequence. In heterothermic ground squirrels (those capable of Tb less than 34 degrees C), a decrease in Ta from 30 degrees to 20 degrees C caused phase delays in activity onset, phase advances in activity termination, and a decrease in duration of the active phase; increases in Ta from 20 degrees to 30 degrees C produced the opposite effect on each of these parameters. The free-running period of the activity rhythm of heterothermic squirrels increased and decreased in response to 10 degrees C decreases and increases in Ta, respectively. Changes in Ta did not affect circadian parameters in homeothermic squirrels. Seasonal variations in circadian organization previously observed in this species appear to reflect the influence of endogenous fluctuations in body temperature. Tissue temperature has a major influence on circadian rhythms of golden-mantled ground squirrels.

Animals↗

Maternal melatonin treatment influences rates of neonatal development of meadow vole pups.

Meadow vole dams, housed in a 14L:10D photoperiod were injected daily 3 h before onset of darkness with 10 micrograms melatonin. Treatment during gestation or lactation produced offspring that exhibited altered somatic, testicular, and pelage growth. Gestational melatonin treatment decreased preweaning weight gain, delayed testicular development, and increased pelage growth in offspring, whereas melatonin treatment during lactation increased pelage depth at weaning and increased post-weaning somatic growth. These results suggest that pre- and postnatal maternal melatonin secretory patterns influence postnatal development of photosensitive traits in offspring.

Animals↗

Estimation of IgE antibody with a nonisotopic technique with no interference of isotypic antibodies.

A modified ELISA was developed to estimate antigen-specific IgE antibody. IgE against ragweed antigen E (AgE) was the model system, and paired pre- and postimmunotherapy sera were evaluated because the latter had been demonstrated to contain significant amounts of IgG antibody. Patients' serum IgE was bound to the surface of wells of a polystyrene microtiter plate previously coated with monoclonal murine antihuman IgE. After washing, AgE conjugated with alkaline phosphatase was added and was specifically bound by IgE. Optical density was recorded after addition of enzyme substrate to the wells and was proportional to the concentration of IgE directed against ragweed AgE in the serum samples. In contrast to many other assay techniques for antigen-specific IgE, interference by specific antibody of other classes cannot occur with this method. Results correlated well with those of a previously described solid-phase radioimmunoassay that required myeloma IgE.

Allergens↗

Structure-activity relationship studies of hemicholinium (HC-3) congeners.

In a continuing investigation of structural requirements for hemicholinium-like activity (inhibition of neuromuscular transmission due to inhibition of uptake of choline into nerve terminals), some additional molecular modifications of hemicholinium ("HC-3"; structure 1) were made. The target compounds were prepared by standard one- or two-step sequences. Noncyclic acetal moieties in general permitted retention of pharmacological activity, as did concomitant replacement of the central biphenyl "spacer" by other bulky cyclic groupings and replacement of the oxazinium rings by piperidine or 4-methylpiperidine. However, these modifications generally produced compounds of a lower potency. Replacement of the biphenyl moiety of HC-3 with polyakylene chains permitted retention of a considerable degree of activity. In these target compounds, the two quaternary nitrogens can exist the same distance apart (approximately 14 A) as in the hemicholinium molecule. The ditertiary amino congener of a pharmacologically active bis-quaternary oxazinium compound was almost completely inactive. To date, only one tertiary amine has been found which displays a significant degree of hemicholinium-like activity.

Animals↗

Vole infant development is influenced perinatally by maternal photoperiodic history.

Vole pups were maintained from the time of conception in the same short-day (SD) photoperiod (10 h light/day, LD 10:14); groups differed only with respect to SD photoperiodic histories of dams before gestation, which simulated those experienced by dams breeding in autumn (SD-2, 2 wk of short days), midwinter (SD-21), or late winter (SD-26). Compared with SD-2 pups, offspring born to SD-26 dams matured more rapidly with respect to body size and reproductive status. Several other somatic and behavioral measures indicated that winter preparedness was greatest in pups whose dams had experienced 2 wk and least in those that had experienced 26 wk of SD treatment before conception. A cross-fostering design, in which pups gestated in long (LD 14:10) or short photoperiods were reared postnatally in the same or opposite day length, indicated that several photoresponsive traits are influenced predominantly by prenatal photoperiod, others by postnatal day length, and others by both photoregimens. Information is communicated to fetuses about the length of time dams have been exposed to short day lengths before mating as well as about the day length prevailing during gestation. The changes induced by the mother in her pups pre- and postnatally likely facilitate adaptation of newly weaned voles to seasonally varying environmental conditions.

Animals↗

Evaluation and management of corticotropin allergy.

Subsequent use of an adrenocorticotropic hormone (ACTH) preparation may be considered in some instances in a patient who has demonstrated a suspected or proven allergic reaction to corticotropin on prior administration. We describe a patient with multiple sclerosis with a history of anaphylaxis to porcine ACTH in whom another course of treatment with ACTH was being considered. The patient had immediate cutaneous reactivity to porcine ACTH but not to the synthetic ACTH peptide, cosyntropin. With a test-dose schedule, we were able to uneventfully administer cosyntropin to the patient. The presence of serum IgE antibody directed against porcine ACTH and absence of IgE antibody against cosyntropin were demonstrated by ELISA technique, corroborating the skin test results. These studies are consistent with previous evidence that immediate hypersensitivity reactions to corticotropin are IgE mediated and support the value of skin testing in the clinical evaluation and management of known or suspected corticotropin hypersensitivity.

Adrenocorticotropic Hormone↗

Prolonged evaluation of patients with corticosteroid-dependent asthma stage of allergic bronchopulmonary aspergillosis.

Eight cases with stage IV allergic bronchopulmonary aspergillosis (ABPA) (corticosteroid-dependent asthma stage) were observed for a total of 82 patient years with individual patients observed for 7 to 19 years (mean 10.2) years. One case is the first case of ABPA diagnosed in the United States in 1967. A second case has been observed through four stages of ABPA. None of these eight cases has demonstrated pulmonary deterioration by clinical, chest roentgenogram, or pulmonary function analysis. After diagnosis, the maintenance dose of prednisone in seven of eight cases was a low to moderate dose alternate-day prednisone. These results suggest that continuous observation and management of episodes of pulmonary consolidation or asthma exacerbations may prevent the progression of ABPA to stage V (fibrotic end stage). The total IgE may remain elevated in these patients, and therapy should not attempt to reduce total serum IgE to normal levels. After prolonged therapy with prednisone for asthma and control of ABPA, the IgE and IgG antibody indices against Aspergillus fumigatus may remain elevated or may be below the levels that are of diagnostic value.

Adolescent↗

Allergic bronchopulmonary candidiasis: case report and suggested diagnostic criteria.

A patient with an illness consistent with allergic bronchopulmonary candidiasis is described. The patient had asthma, atelectatic pulmonary infiltrates on three occasions, immediate cutaneous reactivity as low as 10(-7) (wt/vol) to Candida albicans extract, and precipitating antibody to this organism. C. albicans was the only organism cultured from two bronchial lavage specimens. Total serum IgE was elevated to 5745 ng/ml and decreased rapidly with corticosteroid therapy. Serologic studies were not consistent with allergic bronchopulmonary aspergillosis. Serum IgE to C. albicans, measured by ELISA after adsorption of IgG from the serum samples by incubation with staphylococcal protein A, was found to be 575% to 650% above control values. The serum IgE antibody activity against Candida decreased with clinical improvement after corticosteroid therapy.

Adolescent↗

Influence of daylength experienced by dams on post-natal development of young meadow voles (Microtus pennsylvanicus).

Meadow voles born to dams kept in short days (SD) beginning 5 or 11 weeks before parturition (SD-5, SD-11) had less developed testes, gained weight more slowly and built larger nests than did young gestated and maintained in long days (LD). Pelage development was greater in SD than in LD young at 21 and 45 days of age. At weaning, SD-5 young had less dense fur and shorter guard hairs than did SD-11 young, indicating that the photoperiodic history of dams before insemination affects the post-natal pelage development of their progeny. Short daylengths experienced by dams before mating may facilitate winter preparedness of their offspring.

Animals↗

Role of photoperiod during pregnancy and lactation in the meadow vole, Microtus pennsylvanicus.

The influence of daylength on body mass and food intake of pregnant and lactating voles was tested by comparing animals housed in long versus short daylengths. Pregnancy rates were approximately 50% in long-day females and in voles kept in short days beginning 2 weeks before mating, but were significantly lower in voles preadapted to short days for 8 weeks before mating. Body mass and food intake increased substantially during pregnancy and lactation and the magnitude of the increase was unaffected by daylength; by contrast, body weight was significantly reduced in non-impregnated voles kept in short as compared to long days. The suppressive effects of short photoperiods on body weight were completely counteracted during pregnancy and lactation. Voles that breed during the short days of winter face extreme energetic challenges but the advantages of early breeding appear to justify the costs.

Animals↗

Interaction of daylength and lactation in the control of pelage development and nest-building in female meadow voles (Microtus pennsylvanicus).

Pregnancy and lactation inhibited moult into winter pelage in voles maintained in short daylengths; development of a winter pelage was, however, greatly accelerated once the short-day dams weaned their litters. The presumed elevation of prolactin titres during lactation appears to mask full development and expression of pelage changes induced by short daylengths. Nest-building behaviour, by contrast, was increased in response to short photoperiods and was further augmented during lactation and may thereby facilitate thermoregulation in short-day dams that do not develop a winter pelage.

Animals↗

Structure-activity relationship studies in the hemicholinium ('HC-3') series.

A series of congeners of hemicholinium ('HC-3') has been synthesized, in which the central biphenyl portion of the molecule has been modified, in order to gain insight into possible structural requirements of the biphenyl moiety needed for inhibition of choline uptake into nerve terminals. All molecular modifications resulted in compounds with qualitatively and quantitatively similar pharmacological properties to hemicholinium. It is concluded that the biphenyl portion of the hemicholinium molecule serves as a spacer for maintaining the separation of either the quaternary nitrogens, or the oxazonium rings, at an optimal distance for appropriate interaction with receptor site(s).

Animals↗

Stage V (fibrotic) allergic bronchopulmonary aspergillosis. A review of 17 cases followed from diagnosis.

A review of the records of 17 patients with stage V (fibrotic stage) allergic bronchopulmonary aspergillosis observed since initial diagnosis (mean observation period, 4.9 years) demonstrated that, of the 11 surviving patients, four have very severe respiratory impairment. The other seven patients have mild or moderate functional impairment, but most of these have not shown clinical deterioration during the observation period. The occurrence of new roentgenographic infiltrates after the time of diagnosis was observed in only one patient in this series. Serum IgE and IgG levels against Aspergillus fumigatus, when compared with those of a control pool of serum samples from asthmatic patients with immediate cutaneous reactivity to Aspergillus, were the most useful immunologic studies diagnostically. Lung biopsy specimens obtained in five patients were of relatively little diagnostic value. All patients have required long-term prednisone therapy for control of asthma. Those patients whose forced expiratory volume in 1 s (FEV1) remained less than or equal to 0.8 L after initial corticosteroid treatment demonstrated a poor prognosis. When only moderate lung damage has occurred at the time of diagnosis, a stable subsequent course may be expected even in patients with stage V disease.

Adult↗

Energy metabolism in rat brain in vivo studied by 31P nuclear magnetic resonance: changes during postnatal development.

The energy metabolism in rat brains during postnatal development was followed by in vivo 31P NMR. Using a small surface coil (from several to 10 mm in diameter) placed at the head of a conscious rat, high-energy phosphate compounds in the brain and the steady-state kinetics among them were measured. The cellular contents of some phosphate compounds changed widely during the period of postnatal cell growth from age 10 to 20 days. During the same period, the cellular activity of creatine kinase increased by a factor of more than 5 as measured by a saturation transfer technique. The in vivo value of the creatine/creatine phosphate ratio was estimated from the in vitro value (in perchloric acid extracts), assuming that the in vivo ratio of the creatine and creatine phosphate pool over the ATP and ADP pool was the same as the corresponding in vitro value. From the creatine/creatine phosphate ratio thus obtained, the value of the cytosolic ATP/ADP ratio was estimated for brains of adult rats and neonate rats. Unexpectedly the value in the latter was found to be smaller.

Adenosine Diphosphate↗

Rectus sheath hematoma complicating an exacerbation of asthma.

Hematoma of the rectus sheath is a rare complication of asthma. We describe a case of rectus sheath hematoma precipitated by a paroxysm of cough during an exacerbation of asthma. Diagnosis and management of this clinical entity is discussed.

Abdominal Muscles↗