Biomedical subjects

C D Lothrop

Publications and source records attributed to C D Lothrop.

At least 37 records · Page 2Linked to original sources

PubMed1990

Hormonal abnormalities in Pomeranians with normal coat and in Pomeranians with growth hormone-responsive dermatosis.

Clinical status, skin biopsy specimens, and endocrine function were evaluated in normal-coated Pomeranians (n = 12) and Pomeranians affected with growth hormone (GH)-responsive dermatosis (n = 7), then were compared with values in mixed-breed dog controls (n = 19). All Pomeranians were clinically normal; however, the Pomeranians with GH-responsive dermatosis had bilateral alopecia and hyperpigmentation of the trunk, caudal portion of the thighs, and ventral neck region. Skin biopsy specimens from the affected Pomeranians had decreased-to-normal epidermal thickness and follicular atrophy, compared with normal-coated Pomeranians. Numerous elastin fibers were observed in the skin biopsy specimens of unaffected and affected Pomeranians. Both groups of Pomeranians had normal results of thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) response, adrenocorticotropin (ACTH) stimulation, and dexamethasone suppression testing. There was no significant increase in serum GH concentration in either group of Pomeranians after xylazine or human GH-releasing factor (GHRF) administration, whereas control dogs had significant (P less than or equal to 0.05) increase in serum GH concentration after administration of either agent. Baseline plasma ACTH concentration in unaffected and affected Pomeranians was increased above the normal range (40 to 90 pg/ml). Post-ACTH administration serum progesterone, 17-hydroxyprogesterone, and androgen (dehydroepiandrosterone sulfate or androstenedione) concentrations were consistently high in unaffected and affected Pomeranians, compared with values in control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1990

Plasma von Willebrand factor concentration and thyroid function in dogs.

Plasma von Willebrand factor antigen concentration was determined in 15 dogs with suspected hypothyroidism, in 1 dog with hyperthyroidism, and in 14 euthyroid dogs. The mean +/- SEM von Willebrand factor:antigen concentration in hypothyroid dogs (47.1% +/- 12.6%) was significantly decreased (P less than 0.0005), compared with that in euthyroid dogs (94.7 +/- 5.6%). Four hypothyroid dogs were given thyroxine for 1 month and all 4 had an increase in von Willebrand factor:antigen concentration. The plasma von Willebrand factor:antigen concentration was 200% in the hyperthyroid dog. Seemingly, reduced concentrations of plasma von Willebrand factor:antigen can be found in dogs in association with congenital von Willebrand disease or with von Willebrand disease acquired through hypothyroidism.

Animals↗

PubMed1990

Delayed growth in two German shepherd dog littermates with normal serum concentrations of growth hormone, thyroxine, and cortisol.

Four German Shepherd Dogs from a litter of 10 were evaluated because of postnatal onset of proportionate growth stunting that clinically resembled well-documented hypopituitary dwarfism in that breed. Although 2 pups had histologic evidence of hypopituitarism, the remaining 2 pups had normal serum growth hormone concentration and adrenocorticotropin secretory capability, and normal adrenal function test and thyroid function study results. Furthermore, the initially stunted German Shepherd Dogs grew at a steady rate until at 1 year, body weight and shoulder height approximated normal measurements. Seemingly, delayed growth in these pups may represent one end of a clinical spectrum associated with hypopituitarism in German Shepherd Dogs.

Adrenal Cortex↗

PubMed1990

Effects of recombinant granulocyte colony-stimulating factor treatment on hematopoietic cycles and cellular defects associated with canine cyclic hematopoiesis.

Canine cyclic hematopoiesis (CH) is an autosomal recessive disease of gray collie dogs that is characterized by 14-day cycles of neutropenia, monocytosis, thrombocytosis, and reticulocytosis. Platelets from CH dogs have decreased dense-granule serotonin pools and decreased aggregation responses to collagen, platelet-activating factor (PAF), and thrombin. Recombinant granulocyte colony-stimulating factor (rG-CSF) was administered (5 micrograms/kg, b.i.d.) to four CH and six normal dogs to determine if G-CSF therapy corrected qualitative platelet defects in CH dogs. Neutrophil counts increase to greater than 25,000 cells/microliters within 24 h after starting treatment in all dogs. Treatment with G-CSF blocked neutropenic episodes in the CH dogs. Platelet aggregation, and serotonin content and secretion were significantly (p less than 0.05) decreased in the CH dogs both before and during recombinant human (rh) G-CSF treatment compared to normal dogs. Neutrophil myeloperoxidase, a primary granule enzyme, was significantly (p less than 0.05) decreased in CH dogs and was not corrected by rhG-CSF treatment. Administration of rG-CSF to CH dogs eliminated cell cycles but apparently did not correct cellular defects in CH dogs. Identification of primary biochemical defects in cells from CH dogs may be crucial to investigating the biochemical basis for cyclic hematopoiesis.

Animals↗

PubMed1990

Increased efficiency of gene transfer with retroviral vectors in neonatal hematopoietic progenitor cells.

The retroviral vector N2, which is derived from the Moloney murine leukemia retrovirus, was used to transfer the bacterial NeoR gene (conferring resistance to the neomycin analogue G418) into hematopoietic progenitor cells from fetal, neonatal, and adult dogs and cats. Infection of canine and feline bone marrow cells with the N2 vector resulted in resistance of granulocyte-macrophage colony-forming units (CFU-GM) to G418. Approximately 2%-4% of fetal liver, fetal bone marrow, and adult bone marrow day-7 CFU-GM were resistant to 1.75 mg/ml G418, a dose toxic to cells not expressing the NeoR gene, after infection with the N2 retrovirus. In sharp contrast to the low rate of infectivity of both fetal and adult marrow samples, the mean +/- SD of G418-resistant CFU-GM was 11.7% +/- 14.1% and 14.0% +/- 18.1% for neonatal dog and cat marrow samples, respectively. The neomycin phosphotransferase enzyme activity was detected in G418-resistant CFU-GM, confirming that G418-resistant CFU-GM expressed the NeoR gene. The increased efficiency of retroviral vector-mediated gene transfer into neonatal hematopoietic progenitor cells was not due to an increased fraction of actively dividing cells, as determined by tritiated thymidine suicide. Understanding the basis for increased gene transfer into neonatal hematopoietic progenitor cells may be helpful in designing effective retroviral vectors/gene transfer protocols for gene therapy.

Animals↗

PubMed1989

Hypersomatotropism and insulin-resistant diabetes mellitus in a cat.

In this report, we described the clinical, radiographic, and echocardiographic findings in a cat with hypersomatotropism and insulin-resistant diabetes mellitus. Growth hormone determinations were made because of persistent hyperglycemia despite insulin requirements exceeding 2.2 U/kg of body weight, and the acromegalic features of the cat. Also, the results of a therapeutic trial in which a long-acting analogue of somatostatin was used are discussed.

Acromegaly↗

PubMed1989

Familial immotile-cilia syndrome in English springer spaniel dogs.

A laboratory-maintained colony of English springer spaniel dogs heterozygous for a putative autosomal recessive immotile-cilia syndrome (ICS) has been studied. Matings between dogs thought to be heterozygous for ICS resulted in 22 pups, five (three males and two females) of which were homozygous for ICS. Four of the five ICS-affected dogs had chronic rhinitis and bronchopneumonia. The other dog had a serious nasal discharge and died at 10 days. Four dogs had situs inversus totalis (kartagener syndrome), and the two males of reproductive age were azoospermic. In the two ICS dogs studied for ciliary function, in vivo mucociliary clearance was absent, and in vitro ciliary beat was rarely observed and of low frequency. Scanning and transmission electron microscopy disclosed the same lesions in respiratory cilia from all dogs with ICS, including random orientation and partial outer dynein arm deficiency. Four of five dogs with ICS had dilated lateral ventricles. One female pup with neonatal rhinitis and bronchopneumonia, situs solitus, and dilated lateral ventricles was presumed to be homozygous for ICS, but died without functional or structural confirmation of defective respiratory cilia. An autosomal recessive mode of inheritance for the ciliary defects and respiratory signs of ICS in these dogs is proposed.

Animals↗

PubMed1989

Surface morphology and ultrastructure of normal and cyclic hematopoietic canine bone marrow in long-term liquid cultures.

Long-term liquid cultures of normal and cyclic hematopoietic (CH) dog bone marrow produce committed granulocyte-macrophage progenitor cells (CFU-GM) and differentiated granulocytes for several weeks. Analysis of in situ fixed cultures or of cells harvested from the culture supernatants revealed that the cells had ultrastructure and surface morphology characteristic of immature and mature myeloid cells. The surface morphologies of adherent cells from both normal and CH dogs were similar. The characteristic abnormalities previously reported in neutrophils obtained from CH dogs were not observed in neutrophils obtained from long-term marrow cultures of CH dogs. These results indicate that the cellular abnormalities in the neutrophils of CH dogs may be secondary manifestations of the disease and are not inherent to the pathogenesis of the hematopoietic cells.

Animals↗

PubMed1988

Polycythemia vera in a cat with cardiac hypertrophy.

Polycythemia vera, a rare and poorly documented disease in cats, was diagnosed in a 4-year-old domestic shorthair cat admitted because of seizures. The diagnosis was made on the basis of high PCV, normal serum erythropoietin concentration (as determined by bioassay, using rabbit bone marrow cells), and elimination of secondary polycythemia as a diagnosis. Cardiac hypertrophy, which might have been secondary to blood hyperviscosity, also was diagnosed. The cat has been treated by periodic phlebotomy and has been without clinical signs of disease for more than 20 months.

Animals↗

PubMed1988

Retroviral-mediated gene transfer into hemopoietic cells.

Retroviral vectors have provided a means for the introduction of functioning exogenous genes into the hematopoietic system of whole animals. Although these vectors are quite efficient in the mouse model, when applied to non-murine in vivo systems, the efficiency of gene transfer has diminished to impractical levels. Since in vivo analyses are expensive and time consuming, in vitro models have been developed to speed the evaluation of alternative protocols. Using in vitro colony assays, three approaches were evaluated for their ability to improve the infectivity of hematopoietic progenitor cells with retroviral vectors. Exogenously applied hematopoietic growth factors increased the proportion of hematopoietic colonies in vitro up to an average of 5 fold. When alternative sources of progenitors, such as fetal cord blood, were used, improvements in infection efficiency were also obtained. Finally, evidence was acquired suggesting that xenotropic packaging of vectors also improved infection efficiency.

Animals↗

PubMed1988

Correction of canine cyclic hematopoiesis with recombinant human granulocyte colony-stimulating factor.

Canine cyclic hematopoiesis (CH) is an autosomal recessive disease of gray collie dogs that is characterized by neutropenic episodes at 14-day intervals. The biochemical basis for CH is not known but may involve a regulatory defect of the response to or production of a hematopoietic growth factor. Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to two CH and one normal dog caused a marked leukocytosis (greater than 50,000 WBCs) in all three dogs. The leukocytosis was due largely to a greater than tenfold increase in neutrophils. Less pronounced but significant elevations in monocytes occurred during G-CSF treatment. The elevated WBC count was maintained for more than 20 days in all three dogs, and two predicted neutropenic episodes were prevented in both CH dogs during rhG-CSF treatment. A decline in the WBC count occurred simultaneously in all three dogs during the last five treatment days and was presumably associated with the development of neutralizing antibodies to the heterologous rhG-CSF protein. Bone marrow evaluation indicated that the swings in the myeloid/erythroid progenitor cells that are characteristic of CH were eliminated by rhG-CSF treatment in both CH dogs. These results suggest that the regulatory defect in canine CH can be temporarily alleviated by treatment with rhG-CSF and point to the potential treatment of human cyclic neutropenia with this agent.

Agranulocytosis↗

PubMed1988

Gene transfer into hematopoietic progenitor cells from normal and cyclic hematopoietic dogs using retroviral vectors.

The Moloney murine leukemia retrovirus-derived vector N2 was used to transfer the bacterial NeoR gene (conferring resistance to the neomycin analogue G418) into hematopoietic progenitor cells. Approximately 5% of day seven CFU-GM were resistant to 2,000 micrograms/ml G418, using a supernatant infection protocol in the absence of vector-producing cells. A greater proportion of CFU-GM colonies were recovered relative to uninfected controls as the stringency of selection was diminished. Enzyme activity was detected in drug-resistant colonies, confirming that the resistant colonies obtained after infection with N2 represented cells producing neomycin phosphotransferase. Activity in the CFU-GM colonies approached 50% of that of drug-resistant vector-producing cells on a per cell basis. To test the hypothesis that more rapidly cycling bone marrow cells would be more susceptible to vector infection, we treated progenitor cells obtained from cyclic hematopoietic (CH) dogs with the N2 vector. Despite the increased numbers of hematopoietic progenitor cells obtained from CH dogs, the proportion of G418-resistant CFU-GM did not increase over that obtained with N2-infected normal marrow. These results demonstrate that retroviral vectors can be used to transfer and express exogenous genes in canine hematopoietic progenitor cells.

Animals↗

PubMed1988

Transsphenoidal hypophysectomy in the clinically normal dog.

Pituitary function and short-term clinical effects after transsphenoidal hypophysectomy were investigated in clinically normal dogs. In study I, 8 dogs were given polyionic fluids IV during the first 12 hours after surgery. In study II, 4 dogs were given polyionic fluids IV and glucocorticoid supplementation for 7 days. Pituitary function was assessed by evaluating basal ACTH concentrations and results of a growth hormone stimulation test before and 1 and 12 weeks after hypophysectomy, an ACTH stimulation test, a thyrotropin-releasing hormone-stimulation test, and a modified water deprivation/vasopressin response test before and 1, 4, 8, and 12 weeks after hypophysectomy. Gross and histologic evaluations of the surgery site, thyroid and adrenal glands, and skin were done at 12 weeks after surgery. Four dogs from study I died within 27 hours after hypophysectomy. Postmortem examinations of these dogs revealed liver and lung congestion compatible with circulatory collapse. None of the dogs in study II died. For the surviving dogs in both studies, diabetes insipidus developed immediately after hypophysectomy and resolved within 2 weeks. Hypernatremia also developed immediately after hypophysectomy and resolved by 1 week. Production of ACTH was evident at 1 and 12 weeks after hypophysectomy in all dogs, and results of ACTH stimulation tests after surgery were not notably different from results obtained before surgery. Results of thyrotropin-releasing hormone stimulation and growth hormone-stimulation tests supported the diagnosis of hypothyroidism and hyposomatotropism attributable to hypophysectomy. Histologic examination revealed thyroid atrophy, epidermal and dermal atrophy, and normal adrenal glands in all dogs and remnants of the hypophysis in 2 dogs from study I.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1987

Cyclic hormonogenesis in gray collie dogs: interactions of hematopoietic and endocrine systems.

Cortisol, ACTH, T4, and T3 concentrations were determined in six cyclic hematopoietic (CH) dogs to determine if hormonal cycles were a feature of this hematopoietic disorder. It was determined that there were 12- to 14-day cycles of these hormones in CH dogs. Plasma cortisol and ACTH concentrations peaked 4-8 days after the onset of neutropenia and were concurrent with peak neutrophil counts. The peak ACTH concentration occurred 1-2 days before or concurrent with the cortisol peak concentration. T4 and T3 peak concentrations were opposite the cortisol cycles, and maximal concentrations were seen when cortisol levels were lowest. ACTH, GH-releasing factor and TRH response tests were performed in the CH dogs. No frank deficiencies in hormone production were seen with the ACTH, GH-releasing factor, and TRH responses in CH dogs relative to those in normal dogs. It was concluded that cyclic hormonogenesis is a central feature of CH disease. These findings are the first demonstration of extrahematopoietic system cyclicity in this rare disease and suggest the presence of common regulatory factors in the hematopoietic and endocrine systems.

Adrenocorticotropic Hormone↗

PubMed1987

Prolactin response to thyrotrophin-releasing hormone stimulation in normal and agalactic mares.

Serum prolactin concentration was determined before and after TRH administration to normal mares at 10 months of gestation, 2 and 4 months post partum and during a -7- to +14-day peri-parturient period. The serum prolactin concentration increased significantly (P less than 0.05) at 15, 30 and 60 min after TRH administration in the normal mares regardless of the season of the year, pregnancy or lactation status. However, during the periparturient period, the basal prolactin concentration was increased 4-fold and there was only a marginal increase after TRH administration. Of 9 agalactic mares, 6 had a decreased basal serum prolactin concentration; the other 3 agalactic mares had a normal to increased basal concentration suggestive of a peripheral resistance to prolactin.

Animals↗

PubMed1987

Long-term bone marrow culture systems: normal and cyclic hematopoietic dogs.

A continuous long-term liquid culture in both a micro and macro system that incorporates bone marrow cells from normal and cyclic hematopoietic dogs is described. An adherent layer composed of fibroblasts, endothelial cells, mononuclear phagocytic cells, and fat-containing cells is essential for continuous hematopoiesis. Hematopoiesis was measured by the recovery of the nonadherent cells and the generation of committed granulocyte-monocyte progenitor cells for a period of seven weeks. Optimum growth factors include the use of horse serum, fetal bovine serum, dog serum, hydrocortisone, a 33 degrees C incubation temperature and feeding twice a week. As is true for both human and murine marrow liquid cultures, horse serum and hydrocortisone are essential for development and maintenance of fat-containing cells in the described systems. Both factors are important in hematopoiesis but their respective roles have not been defined. Normal and cyclic hematopoietic dogs bone marrow cells are comparable in their ability to establish long-term cultures. The micro-method (Linbro-well culture) gave similar results in maintaining hematopoiesis as did a macromethod (flask culture).

Animals↗

PubMed1986

Feather and beak dystrophy and necrosis in cockatoos: clinicopathologic evaluations.

Several species of imported and captive-bred southeast Asian cockatoos with feather and beak disease (FBD) were evaluated. In recently emerging stained feathers from affected birds, intracytoplasmic magenta to basophilic inclusions of various sizes were found in macrophages and basophil-like cells within the pulp and feather epidermis. Occasionally, amphophilic intranuclear inclusions were seen within degenerated feather epidermal cells. On the basis of electron microscopic findings, intracytoplasmic inclusions were not membrane bound and consisted of crystalline arrays of viral particles (17 to 22 nm in diameter). On the basis of size and conformation, viral particles most closely resembled those of parvovirus or picornavirus. Consistent hematologic or serum enzyme differences were not found among affected or healthy cockatoos. Compared with findings in healthy cockatoos, cockatoos with FBD had significantly lower serum protein concentrations, and results of serum protein electrophoresis indicated that birds with FBD had significantly lower concentrations of prealbumin and gamma-globulin fractions. Mean pre- and post-ACTH plasma corticosterone concentrations of cockatoos with FBD were not significantly different from those of healthy cockatoos. In 8 of 9 affected cockatoos evaluated, serum T4 concentrations before and after thyrotropin stimulation were considered normal.

Animals↗

PubMed1986

Hyperprogesteronemia associated with Sertoli cell tumor and alopecia in a dog.

Hyperprogesteronemia was found in a dog with alopecia and Sertoli cell tumor. Alopecia began in the lumber areas; the entire coat was dull and dry, and epilated easily. The only laboratory abnormalities were high serum progesterone concentration and incomplete suppression of cortisol after low-dose dexamethasone administration. The hair regrew after castration, and the progesterone concentration decreased toward normal.

Adrenocorticotropic Hormone↗