Repeated Famotidine Administration Results in a Diminished Effect on Intragastric pH in Dogs.

BACKGROUND: Famotidine is an acid suppressant commonly administered to dogs. Prolonged famotidine use in people results in decreased efficacy, but the effect in dogs is unknown. HYPOTHESIS/OBJECTIVES: To compare the effect of repeated oral administration of famotidine or placebo on intragastric pH and serum gastrin in dogs. We hypothesized that famotidine would have a diminished effect on intragastric pH on day 13 compared to day 1. ANIMALS: Six healthy adult colony Beagles. METHODS: Randomized, 2-factor repeated-measures crossover design. All dogs received oral placebo or 1.0 mg/kg famotidine q12h for 14 consecutive days. Intragastric pH monitoring was used to continuously record intragastric pH on treatment days 1-2 and 12-13. Mean pH as well as mean percentage time (MPT) that intragastric pH was ≥3 or ≥4 were compared between and within groups by analysis of variance. Serum gastrin was measured on days 0, 3, and 12 for each treatment. RESULTS: Continued administration of famotidine resulted in a significant decrease in mean pH, MPT ≥3, and MPT ≥4 (P < .0001) on day 12 and 13. This resulted in a mean decrease in pH by 1.63 on days 12 and 13 compared to days 1 and 2. Furthermore, a mean decrease of MPT ≥3 and MPT ≥4 by 33 and 45% was observed for the same time period, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Continued administration of famotidine results in a diminished effect on intragastric pH in dogs. Caution is advised when recommending long-term, daily oral administration of famotidine to dogs.

Hepatic lesions in 90 captive nondomestic felids presented for autopsy.

Hepatic lesions in nondomestic felids are poorly characterized. The purpose of this study was to evaluate hepatic lesions in 90 captive, nondomestic felids including tigers, cougars, and lions. Hepatic lesions were histologically characterized as vacuolar change (lipidosis or glycogenosis), biliary cysts, biliary hyperplasia, hepatitis, necrosis, neoplasia, fibrosis, veno-occlusive disease, cholestasis, hematoma, congestion, or hemorrhage. Stepwise logistic regression analyses were performed for vacuolar change, benign biliary lesions, hepatitis, lipogranulomas, extramedullary hematopoiesis, and hepatic stellate cell hypertrophy and hyperplasia, with species as the outcome variable. Ninety cats met the inclusion criteria. Seventy livers (78%) contained 1 or more lesions. Hepatocellular vacuolar change (41/90 [46%]) was the most common lesion overall. Extramedullary hematopoiesis, lipogranulomas, and hepatic stellate cell hyperplasia were also common. One snow leopard had veno-occlusive disease. Tigers were more likely than other felids to have no significant hepatic histologic lesions (odds ratio [OR], 12.687; P = .002), and lions were more likely to have biliary cysts (OR, 5.97; P = .021). Six animals (7%) died of hepatic disease: cholangiocellular carcinoma (n = 2) and 1 each of hepatic lipidosis, hepatocellular necrosis, pyogranulomatous hepatitis, and suppurative cholecystitis. Hepatocellular iron and copper accumulations were present in 72 of 90 (80%) and 10 of 90 (11%) sections, respectively. Sinusoidal fibrosis was common (74/90 [82%]) and primarily centrilobular (65/74 [88%]). Hepatocellular iron, copper, and fibrosis were not significantly associated with hepatic lesions. Primary hepatic disease was not a common cause of death in nondomestic felids in this study.

COX-2 and c-kit expression in canine gliomas.

Gliomas are among the most common primary neural tumours of dogs. Cyclooxygenase-2 (COX-2) and c-kit overexpression are associated with increased aggressiveness of gliomas and decreased survival in human beings. COX-2 is the inducible form of cyclooxygenase, which catalyzes prostaglandin formation and may increase tumour proliferation and angiogenesis. C-kit is a tyrosine kinase receptor involved in normal cell physiology; c-kit is upregulated in some canine tumours. In this retrospective study, 20 canine gliomas were identified: 11 (55%) oligodendrogliomas, including 1 anaplastic variant; 1 (5%) oligoastrocytoma; and 8 (40%) astrocytomas, of which 2 were glioblastoma multiforme. None of the gliomas expressed COX-2. None of the gliomas were immunoreactive for c-kit, although all three high-grade tumours had intramural vascular expression. Consequently, COX-2 inhibitors would likely be ineffective against canine gliomas. C-kit inhibitors may have an anti-angiogenic effect in high-grade gliomas, but would likely be ineffective in low- and medium-grade tumours.

Renal lesions of nondomestic felids.

To comprehensively evaluate the occurrence of renal lesions in a variety of nondomestic felids, necropsy cases from 1978 to 2008 were reviewed from a municipal zoo and a large cat sanctuary for those in which the kidneys were examined histologically. Seventy exotic felids were identified (25 tigers, 18 lions, 6 cougars, 5 leopards, 3 snow leopards, 3 clouded leopards, 3 Canadian lynx, 2 ocelots, 2 bobcats, 2 cheetahs, 1 jaguar), and their histologic renal lesions were evaluated and compared. The most common lesion was tubulointerstitial nephritis (TIN); 36 of 70 (51%) cats were affected to some degree. Lymphocytic interstitial nephritis was the most common lesion in the tigers (9 of 25, 36%) and was rarely seen in other species. Although the renal pelvis was not available for all cats, 28 of 47 (60%) had some degree of lymphocytic pyelitis. There was no significant association between the presence of pyelitis and that of TIN. Only 1 cat had pyelonephritis. Renal papillary necrosis was present in 13 of 70 (19%) cats and was significantly associated with historical nonsteroidal anti-inflammatory drug treatment (odds ratio, 7.1; 95% confidence interval, 1.9 to 26.8). Only 1 cat (lion) had amyloid accumulation, and it was restricted to the corticomedullary junction. Primary glomerular lesions were absent in all cats. Intraepithelial pigment was identified in many of the cats but was not correlated with severity of TIN. Despite several previous reports describing primary glomerular disease or renal amyloidosis in exotic felids, these lesions were rare to absent in this population.

A retrospective study of eyelid tumors from 43 cats.

Submissions to the University of Tennessee pathology service from June 1999 to June 2008 were searched for feline cases of tumors involving the eyelids or nictitans. Forty-three tumors were identified. The average age at diagnosis was 10.4 years. Significantly more males than females had eyelid tumors. There were 12 squamous cell carcinomas (SCCs), 11 mast cell tumors (MCTs), 6 hemangiosarcomas (HSAs), 4 adenocarcinomas (ACAs), 3 peripheral nerve sheath tumors (PNSTs), 3 lymphomas, 3 apocrine hidrocystomas (AHCs), and 2 hemangiomas. Cats with MCTs were significantly younger than cats with all other tumor types combined. In contrast, cats with SCCs were significantly older than cats with other tumor types. The HSAs and SCCs were significantly more likely than other tumors to occur in nonpigmented areas. The MCTs, HSAs, AHCs, and hemangiomas did not recur after surgical excision. In contrast, the lymphomas, ACAs, SCCs, and PNSTs frequently recurred and/or resulted in death or euthanasia of the cat. The SCCs were significantly more likely to recur than the MCTs. The average survival time for cats with SCCs was 7.4 months. Although eyelid MCTs have been reported in cats, the prevalence in this study is much higher than previously described.

Uveal spindle cell tumor of blue-eyed dogs: an immunohistochemical study.

Immunohistochemical techniques were used to investigate the origin of a spindle cell tumor in the anterior uveal tract of dogs and the influence of ultraviolet radiation on the development of this tumor. Thirteen tumors were identified from the 4,007 canine ocular samples examined at the Comparative Ocular Pathology Laboratory of Wisconsin between 1978 and 2005. Siberian Husky and Siberian Husky mix dogs were overrepresented (10/13 dogs, overall median age 10 years). Light microscopic evaluation (all dogs) and electron microscopy (2 dogs) were performed. Immunohistochemical staining included alpha-smooth muscle actin (SMA), vimentin, S-100, desmin, glial fibrillary acidic protein (GFAP), Melan A, microphthalmic transcription factor (MITF-1), protein gene product 9.5 (PGP 9.5), laminin, gadd45, p53, proliferating cell nuclear antigen (PCNA), anti-UVssDNA (antibody for detection of (6-4)-dipyrimidine photoproducts), and telomerase reverse transcriptase (TERT). All tumors occurred in the iris with or without ciliary body involvement and were composed of spindle cells arranged in fascicles and whorls (variable Antoni A and B behavior). All tumors were positive when immunostained for vimentin and S-100. Nine of 13 tumors exhibited GFAP immunopositivity. All tumors were negative for SMA, desmin, Melan A, and MITF-1. Tumors were variably positive for PGP 9.5, laminin, gadd45, p53, PCNA, anti-UVssDNA, and TERT. Electron microscopy revealed intermittent basal laminae between cells. These tumors are morphologically and immunohistochemically most consistent with schwannoma. The relationship between spindle cell tumors of the anterior uvea of dogs, altered neural crest, blue iris color, and ultraviolet radiation has not yet been fully elucidated.

Soil warming and carbon-cycle feedbacks to the climate system.

In a decade-long soil warming experiment in a mid-latitude hardwood forest, we documented changes in soil carbon and nitrogen cycling in order to investigate the consequences of these changes for the climate system. Here we show that whereas soil warming accelerates soil organic matter decay and carbon dioxide fluxes to the atmosphere, this response is small and short-lived for a mid-latitude forest, because of the limited size of the labile soil carbon pool. We also show that warming increases the availability of mineral nitrogen to plants. Because plant growth in many mid-latitude forests is nitrogen-limited, warming has the potential to indirectly stimulate enough carbon storage in plants to at least compensate for the carbon losses from soils. Our results challenge assumptions made in some climate models that lead to projections of large long-term releases of soil carbon in response to warming of forest ecosystems.

Angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter review and an algorithm for airway management.

Angioedema is a nonpitting edema of which the presentation ranges from benign facial swelling to airway obstruction managed by intubation or tracheotomy. The presentation of this disease is reviewed, and a treatment algorithm based on initial signs and symptoms is proposed for proper airway management. We performed a retrospective review of 108 patients treated in 2 tertiary care centers in the Washington, DC, area over a 5-year period. Ninety-eight patients (90.7%) were African-American, and 81 (75%) were female. Seventy-four patients (68.5%) were taking angiotensin-converting enzyme inhibitors (ACEIs). A classification system was developed based on the location of the edema at initial presentation: 1) isolated facial swelling and oral cavity edema, excluding the floor of the mouth; 2) floor of mouth and/or oropharyngeal edema, and 3) oropharyngeal edema with glottic and/or supraglottic involvement. Fourteen patients (13%) needed airway intervention, 2 of whom underwent a cricothyrotomy after a failed intubation attempt. Eleven (78.6%) were taking ACEIs. The indication for each intubation was massive tongue and floor of mouth edema. The patients were extubated 48 to 72 hours later. No patient demonstrated symptom progression after medical treatment was initiated. Therapy included discontinuation of the ACEI or other inciting agent, a high-humidity face tent, an initial dose of intravenous antihistamines, and a continued course of intravenous steroids. Within 48 hours, most patients had a resolution of their edema. Only cases of significant tongue and oropharyngeal edema took longer than 48 hours to resolve. The ACEIs are a common cause of angioedema. Left untreated, angioedema may progress to involve the oropharynx and supraglottis, resulting in a life-threatening airway compromise. Marked floor of mouth and tongue edema are the indications for airway intervention. An algorithm based on the initial presentation is essential for proper airway and patient management. Once treatment has begun, angioedema is nonprogressive and often resolves within 24 to 48 hours.

Planned neck dissection for advanced primary head and neck malignancy treated with organ preservation therapy: disease control and survival outcomes.

BACKGROUND: The role of planned neck dissection after organ preservation therapy with radiotherapy or chemotherapy/radiotherapy for advanced head and neck cancers presenting with clinically positive neck disease is still being elucidated. The aim of this study is to review the outcomes of such patients treated by organ preservation therapy at our institution. METHODS: A retrospective chart review of 33 patients who underwent planned neck dissections after organ preservation therapy for advanced primary head and neck malignancy. Endpoints measured were disease-free survival and local, regional, and distant control. SETTING: Tertiary metropolitan medical center. RESULTS: Two-year actuarial disease-free survival was 61%, and neck control was 92%, with only two failures in the neck. The use of neoadjuvant chemotherapy and total dose of radiotherapy did not correlate with neck control or disease-free survival. The presence of pathologically positive nodal disease at the time of neck dissection did not correlate with recurrent neck disease, but was a predictor of local recurrence (p = .0086). CONCLUSIONS: Our data suggest that for patients undergoing planned neck dissection after organ preservation therapy, neck control is obtained in almost all cases. The presence of pathologically positive nodal disease at the time of surgery may have implications for the incidence of local recurrence.

Ultrasound-guided fine-needle aspiration and thyroid disease.

BACKGROUND: Fine-needle aspiration represents a critical diagnostic test in determining proper management of thyroid disease and the use of ultrasound-guided fine-needle aspiration (USGFNA) has increased over the years. METHODS: A retrospective chart review of patients undergoing USGFNA. Two hundred fifteen patients underwent 234 procedures with 362 nodules aspirated within a 2 (1/2)-year period. RESULTS: The mean ages of women and men were 51.9 and 57.8, respectively. The average size of nodules was 2.1 cm. A difficult to assess gland or nodule was the most common indication for USGFNA (33%). The sensitivity was 88.2%, specificity was 80.0%, the PPV was 65.2%, the negative predictive value was 94.1%, and the accuracy was 82.5%. The cancer yield, inadequacy, and complication rates were 44%, 10.5%, and 8.5%, respectively. CONCLUSIONS: USGFNA aspiration is a safe and effective diagnostic modality in the management of thyroid disease, especially for nodules that are difficult to palpate.

The role of radioactive iodine in salivary gland dysfunction.

The use of radioactive iodine has become an important adjunct to the treatment of thyroid cancer. Many normal tissues--including salivary glands, gastrointestinal mucosa, gonads, and lactating breast tissue--have the ability to concentrate radioactive iodine under normal circumstances. Although the mechanism is just beginning to be elucidated, it is this ability that might contribute to the immediate and long-term complications associated with radioactive iodine treatment. In some patients, the salivary complications can be permanent and might compromise daily functioning. In this article, we examine the salivary gland complications associated with radioactive iodine therapy, and we suggest potential protective mechanisms to circumvent these problems.

Complications from planned, posttreatment neck dissections.

OBJECTIVE: To report the complication rate from planned, posttreatment neck dissections in patients who show control of primary squamous cell carcinoma by chemotherapy and radiotherapy or radiotherapy alone. DESIGN: Retrospective review of case series. SETTING: Georgetown University Medical Center, Washington, DC. PATIENTS: Thirty-four patients with clinically positive neck disease treated with organ preservation therapy for squamous cell carcinoma of the head and neck. INTERVENTIONS: Planned neck dissection after treatment with chemotherapy and radiotherapy or radiotherapy alone. MAIN OUTCOME MEASURE: Perioperative complications. RESULTS: Forty-one neck dissections were performed on 34 patients. Complications were seen in 13 (38%) of 34 patients and 15 (37%) of 41 neck dissections. Wound complications occurred in 9 (22%) of 41 dissections. Neck dissection complication rate did not correlate with previous use of chemotherapy or with the use of brachytherapy at the primary site at the time of the neck dissection. Preoperative radiotherapy dose greater than 70 Gy was associated with complications in 58% vs 29% when preoperative dose was less than 70 Gy (P = .09). This trend was reflected primarily in wound complications (42% vs 14%; P = . 10) and reached significance for skin flap necrosis (33% vs 0%; P = .005). Other factors that were associated with increased complications were preoperative albumin level less than 38 g/L and early neck drain removal. CONCLUSIONS: The complication rate associated with planned posttreatment neck dissection is similar to that previously reported for neck dissection. Wound complications are more common when higher preoperative radiotherapy doses are used.

Association between expression of glutathione-associated enzymes and response to platinum-based chemotherapy in head and neck cancer.

We examined the correlation between response to platinum-based chemotherapy and expression of glutathione S-transferase (GST), gamma-GGT (both by immunohistochemistry) and gamma-GCS (by in situ hybridization) in 51 patients with head and neck cancer, who received a total of 56 courses of chemotherapy. The overall response rate for the 56 chemotherapy treatment courses was 48%. The overall response rate (CR, PR) for patients with low GST scores was 88% (21 of 24), while among the patients with high GST scores, the overall response rate was 19% (6 of 32, P = 0.001). Patients with a low GST score were 4.7 times more likely to respond to chemotherapy than patients with high GST scores. GST scores corresponded to response in 84% of cases. Among 33 patients treated with chemotherapy for relapsed disease, the overall response rate for patients with low GST score was 70% (7 of 10), while among the patients with high GST scores, the overall response rate was 8.7% (2 of 23), P < 0.001). In contrast, both gamma-GCS and gamma-GGT showed a range of expression in these samples, but there was no significant correlation with treatment response. We conclude that GST expression correlates well with response to platinum based chemotherapy in head and neck cancer.

Earlier thermoregulation and consequences for pup growth in the Siberian versus Djungarian dwarf hamster (Phodopus).

In spite of the shared reproductive timetable and phenotypic similarity of the two Phodopus species, previous studies had suggested that P. sungorus pups might thermoregulate at an earlier age and might experience decreases in growth rate as a consequence of that energetic demand. The current study investigated thermogenesis and thermoregulation in single pups and huddles separated from adults. Thermoregulation was earlier (Day 9 vs Day 12 for the earliest individuals) in P. sungorus than in P. campbelli and occurred at a lower body weight (6 vs. 8 g). Earlier development of insulating pelage in P. sungorus was not responsible. Both guard and underhair components of the pelt were completed earlier in P. campbelli development. Pup weights from five independent studies of each species were used to compare patterns of growth. Although birthweights were similar, P. sungorus pups grew faster during early lactation. Nest temperatures were probably involved in that faster growth. Maternal hyperthermia raised nest temperatures > or =4 degrees C above nonbreeding levels and left P. sungorus huddles 1.0 degrees C warmer than P. campbelli huddles throughout lactation. Comparisons between studies also suggested that laboratory conditions adversely affected pup growth in each species. In P. campbelli, cool ambient temperatures and biparental care improved early growth. In P. sungorus, providing fresh apple as a water source prevented a major decline in pup growth rate during mid to late lactation. Thus, as predicted, P. sungorus pups grow faster, thermoregulate earlier, and weigh more at Day 18 (when water is available to the pups).

Pneumomediastinum in a high school football player: a case report.

OBJECTIVE: To provide athletic trainers with information about the mechanism, evaluation, and treatment of pneumomediastinum. BACKGROUND: This is a case study of a high school football player who suffered pneumomediastinum as a result of a flat-handed thump to his sternal area during a blocking drill. Pneumomediastinum is a relatively rare occurrence in sports. Common mechanisms include direct blunt trauma, vomiting, sneezing, Valsalva maneuver, and forceful coughing. Typical signs and symptoms include chest pain, dyspnea, tenderness, crepitus in the neck that can be aggravated with swallowing, and a positive Hamman's sign with auscultations. DIFFERENTIAL DIAGNOSIS: Pneumothorax, pneumopericardium, sternal contusion, rib fracture, upper respiratory infection, and myocardial infarction. TREATMENT: Conservative management includes restriction from athletic activities, prophylactic antibiotics, and sleeping in a semireclined position. Surgical repair of the defect may be indicated if repeat radiographs fail to show improvement after 1 week. UNIQUENESS: It is rare that a relatively light blow through shoulder pads would result in a pneumomediastinum. Review of the literature does not include this athlete's symptoms of congestion, nasal voice, or sore throat as typical signs of pneumomediastinum. CONCLUSIONS: The literature indicates that an uncomplicated pneumomediastinum will typically resolve in 2 weeks' time. In this case, symptomatic evaluation warranted only 1 week of rest before the athlete was allowed to return to full activity.

Length of delay to birth of a second litter in dwarf hamsters (Phodopus): evidence for post-implantation embryonic diapause.

In Phodopus, all first litters are born after an 18 (or 19) day gestation. Birth of subsequent litters conceived during a postpartum estrus is routinely, but not always, delayed beyond 18 days. With an interval from first mating to birth of a second litter of as little as 36 days, Phodopus have the most compressed reproductive cycle of any eutherian mammal. Although pups of the Siberian hamster P. sungorus gain thermal independence from maternal care faster than pups of the Djungarian hamster P. campbelli, no species difference in the extent of delay to second litters was found. However, poor growth of first litter pups as a result of unintentional limitation of water bottle access increased delays before birth of a second litter in P. sungorus. Weight of pups in the first litter was a good predictor of the length of delay. In P. campbelli, females with large pups early in lactation were the only ones to deliver a second litter without delay, and short delays enhanced weaning weights for pups in the first litter. Patterns in P. sungorus were similar. The timing of the delay in second litters was investigated in P. campbelli. Delayed implantation during second pregnancies was common. Postimplantation embryonic diapause occurred in 43% of females following unilateral ovariohysterectomy on day 8 of a first pregnancy. As pup growth curves also implicated a postimplantation embryonic diapause, Phodopus may be the only known mammalian genus outside the order Chiroptera in which postimplantation diapause can occur.

Glutathione content but not gamma glutamyl cysteine synthetase mRNA expression predicts cisplatin resistance in head and neck cancer cell lines.

PURPOSE: To correlate cellular glutathione content and gamma-glutamyl cysteine synthetase (gamma GCS) mRNA expression with cisplatin sensitivity in a panel of seven head and neck squamous cancer cell lines. METHODS: Cisplatin IC50 was determined for each cell line using a sodium tetreazolium (XTT) assay. Cellular glutathione content was measured by using a previously reported enzymic method. gamma GCS mRNA expression was measured using an RNase protection assay. RESULTS: Total cellular glutathione was an excellent predictor of cisplatin sensitivity in this series of cell lines. The IC50 for cisplatin in the cell line with the highest glutathione concentration was approximately 90 times higher than in the cell line with the lowest glutathione concentration. Regression analysis showed a highly statistically significant positive correlation between cisplatin IC50 and cellular glutathione (coefficient of determination R2 = 0.81, P = 0.0012). Some-what surprisingly, in contrast to previous studies in ovarian cancer, gamma GCS mRNA expression in these cell lines was not significantly predictive of either total cellular glutathione or cisplatin sensitivity (R2 = 0.005, P = 0.84). As expected, treatment of resistant cell lines with buthionine sulfoximine resulted in decreased cellular glutathione and enhanced cisplatin sensitivity. CONCLUSIONS: Our results suggest that glutathione may be an important determinant of cisplatin sensitivity in clinical head and neck cancer. Since cisplatin is the most active chemotherapy drug for the treatment of this disease, this correlation may have important clinical relevance. The lack of correlation between glutathione level and gamma GCS expression suggests that salvage or alternate synthetic pathways may be critical in these cells.

Immunohistochemical staining for glutathione S-transferase predicts response to platinum-based chemotherapy in head and neck cancer.

The glutathione S-transferases (GSTs) play an important role in the cell's defense against toxic substances. The GSTs are a family of enzymes produced by several genes that interact with distinct but overlapping substrates and that may play a role in resistance of tumor cells to several chemotherapeutic agents. We examined the correlation between expression of GSTs determined by immunohistochemistry and clinical response to platinum-based chemotherapy in 51 patients with head and neck cancer, who received a total of 56 courses of chemotherapy. The overall response rate for the 56 chemotherapy treatment courses was 48%. The overall response rate (complete response + partial response) for patients with low GST scores was 88% (21 of 24), whereas among the patients with high GST scores, the overall response rate was 19% (6 of 32; P = 0.001). Patients with a low GST score were 4.7 times more likely to respond to chemotherapy than patients with high GST scores. GST scores corresponded to response in 84% of cases. Among 23 patients treated with neoadjuvant chemotherapy, the overall response rate for patients with low GST scores was 100% (14 of 14), whereas among the patients with high GST scores, the overall response rate was 44% (4 of 9; P = 0.002). Among 33 patients treated with chemotherapy for relapsed disease, the overall response rate for patients with low GST scores was 70% (7 of 10), whereas among the patients with high GST scores, the overall response rate was 8.6% (2 of 23; P < 0.001). We conclude that GST expression correlates well with response to platinum-based chemotherapy in head and neck cancer.

Ontogeny of thermoregulation in the Djungarian hamster (Phodopus campbelli).

At birth, altricial Djungarian hamster pups require exogenous heat to grow and gain little benefit from huddling with their littermates. By day 6 huddled pups begin effective thermogenesis although isolated pups do not show spontaneous increases in temperature until day 9. On day 12, isolated pups can resist cooling for short periods of time and huddles do not cool within a 15 min test. By day 15, isolated pups can thermoregulate, although at a lower core body temperature than is typical of adults, and both huddling contact with littermates and direct contact with the dam are reduced. At weaning, pups are effectively thermally independent. This ontogeny is correlated with behavioral, morphological and physiological changes during pup development including brown adipose tissue (BAT) thermogenesis, pelage development and body size. The onset of thermogenesis, and then thermoregulation, causes temporary reductions in pup growth rate on days 6 and 7 and again on days 12 and 13. Body weight, rather than pup age, appears critical for independent thermoregulation. These results are discussed relative to the extent of maternal hyperthermia and the physiological demands of the concurrent gestation characteristic of reproduction in Djungarian hamsters.

Solution NMR structure of the major cold shock protein (CspA) from Escherichia coli: identification of a binding epitope for DNA.

Sequence-specific 1H and 15N resonance assignments have been determined for the major cold shock protein (CspA) from Escherichia coli with recently developed three-dimensional triple-resonance NMR experiments. By use of these assignments, five antiparallel beta-strands were identified from analysis of NMR data. Strands 1-4 have a classical 3-2-1-4 Greek key beta-sheet topology and there are two beta-bulges, at positions Lys10-Trp11 and Gly65-Asn66. Three-dimensional structures of CspA were generated from NMR data by using simulated annealing with molecular dynamics. The overall chain fold of CspA is a beta-barrel structure, with a tightly packed hydrophobic core. Two-dimensional isotope-edited pulsed-field gradient 15N-1H heteronuclear single-quantum coherence spectroscopy was used to characterize the 15N-1H fingerprint spectrum with and without a 24-base oligodeoxyribonucleotide, 5'-AACGGTTTGACGTACAGACCATTA-3'. Protein-DNA complex formation perturbs a subset of the amide resonances that are located mostly on one face of the CspA molecule. This portion of the CspA molecular surface includes two putative RNA-binding sequence motifs which contribute to an unusual cluster of eight surface aromatic side chains: Trp11, Phe12, Phe18, Phe20, Phe31, His33, Phe34, and Tyr42. These surface aromatic groups, and also residues Lys16, Ser44, and Lys60 located on this same face of CspA, are highly conserved in the family of CspA homologues. These isotope-edited pulsed-field gradient NMR data provide a low-resolution mapping of a DNA-binding epitope on CspA.