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Biomedical subjects

J E Fisher

Publications and source records attributed to J E Fisher.

At least 19 recordsLinked to original sources
PubMed1992

Eosinophilic cystitis in children.

A case of eosinophilic cystitis in a child is presented and the pediatric literature reviewed. The etiology of this condition is still unknown. Mean age of children with eosinophilic cystitis is 5.9 years. Black children appear to be more affected than white children, with a male preponderance. Hematuria and dysuria are the most common symptoms. The diagnosis of eosinophilic cystitis is made by cystoscopy with biopsy. The disease appears self-limited with its course unaltered by antibiotics. Recurrence of eosinophilic cystitis is possible.

Adolescent↗
PubMed1992

Concentrations of parathyroid hormone-related protein in rat milk change with duration of lactation and interval from previous suckling, but not with milk calcium.

PTH-related protein (PTHrP) is found in high concentrations in the milk of various mammals. However, little is known about the regulation of PTHrP production or the physiological role(s) of PTHrP in the mammary glands. To address these questions, we examined in lactating rats 1) the longitudinal changes in PTHrP concentrations in milk and PTHrP mRNA levels in the mammary glands throughout lactation, 2) the effects of the nonsuckling interval on milk PTHrP concentration, and 3) the correlation between PTHrP and calcium concentrations in milk. PTHrP concentrations in milk, measured by RIA and in vitro bioassay, increased with the duration of lactation. The maximal concentrations of PTHrP (observed between days 19-21 of lactation in rats milked serially) were 4.8- to 8.0-fold higher than the concentrations on day 7. PTHrP mRNA levels in the mammary glands also increased during the late stages of lactation. The longitudinal changes in calcium concentrations in milk were small and did not parallel the changes in PTHrP. When pups were removed from the mother for 4-24 h, milk PTHrP decreased while calcium increased in a time-dependent manner. As a whole, calcium concentrations in milk did not correlate with PTHrP throughout lactation. These data suggest that the production and secretion of PTHrP into milk are regulated independently of the other major milk proteins by a factor(s) that changes with progression of lactation and in relation to suckling status.

Animals↗
PubMed1991

The magnocellular and parvocellular divisions of the monkey subthalamic nucleus as revealed by cluster analysis of neuronal sizes.

Cluster analysis of neuronal somal sizes in the subthalamic nucleus of rhesus monkeys from newborn to adult age allows the segregation of two territories with predominance of small and large cells, respectively. The topographic distribution of the 'parvocellular' and 'magnocellular' segments is similar when samples are obtained from coronal, horizontal and sagittal series of sections. The parvocellular component occupies the rostral pole, the entire rostrocaudal extent of the medial tip and dorsomedial border, and probably also the caudal cap. The magnocellular segment is in the central core extending to the ventrolateral border except for the medial tip. These findings and their correlation with the results of other morphologic and physiologic studies allow the following conclusions. (1) The monkey subthalamic nucleus contains at least two differentially distributed cell subpopulations. (2) The magnocellular division is more related to the pallido-subthalamic-pallidal loop involving the lateral pallidal segment. (3) The parvocellular division appears strategically located to control the pallidal output to diencephalic and mesencephalic targets. (4) Cluster analysis can reveal the existence of more than one neuronal population in a particular brain structure where an overall unimodal distribution of cell sizes may suggest the presence of a single type.

Aging↗
PubMed1991

Solid-phase synthesis and biologic activity of human parathyroid hormone (1-84).

We have chemically synthesized the full-length, 84 amino acid, human parathyroid hormone (hPTH) on a greater than 100 mg scale by the Merrifield solid-phase technique of stepwise peptide synthesis using a benzhydrylamine support. The peptide was purified by high-performance liquid chromatography and found to be greater than 96% pure. The authenticity or the sequence of the synthetic peptide was confirmed by repetitive Edman degradation. Furthermore, tryptic digestion of hPTH generated the predicted fragments. The synthetic full-length hormone was evaluated for biologic activity in assays of PTH receptor binding and stimulation of adenylate cyclase activity (using bovine renal cortical membranes and rat and human bone cells). Synthetic hPTH (1-84) was found to be highly potent in binding to PTH receptors (Kb = 1-25 nM) and stimulating adenylate cyclase (Km = 1-14 nM). The availability of significant quantities of synthetic full-length hPTH and future analogs will permit widespread use in multiple in vitro and in vivo assays to delineate their spectrum of biologic properties. Available supplies of the synthetic hormone will also enable evaluation of the effectiveness of PTH antagonists at inhibiting the action of native sequence hormone at its receptors.

Adenylyl Cyclases↗
PubMed1991

Constitutional extra chromosomal element in a family with Wilms' tumor.

We report the presence of an extra chromosomal element in a family with Wilms' tumor (WT). This family has three children, two of whom were affected. One son, the proband, had bilateral and one daughter had unilateral WT. The first child, the father, and the mother did not have WT. The son with bilateral WT had a ring chromosome (R) both in the lymphocytes as well as in the kidney tissue. The size of the ring varied considerably from cell to cell. The daughter with unilateral WT had an abnormal clone containing a small chromosomal ring (r) in phytohemagglutinin (PHA)-stimulated and Epstein-Barr virus (EBV)-transformed lymphocytes. The mother had a karyotype similar to that of the daughter with WT. We hypothesize that the proband's ring chromosome could be the amplified form of the r inherited from the mother. Chromosome 11 was cytogenetically normal in all the cells examined of the affected children and the unaffected mother. In situ hybridization with a centromere-specific DNA cocktail indicated dispersed centromeric DNA both in r and R.

Adult↗
PubMed1991

Suckling-mediated increases in urinary phosphate and 3',5'-cyclic adenosine monophosphate excretion in lactating rats: possible systemic effects of parathyroid hormone-related protein.

Earlier studies have shown that lactation-induced bone loss in the rat is both PTH- and vitamin D-independent and have suggested the involvement of another, as yet unidentified, factor(s) in the altered calcium metabolism which accompanies lactation. In the present study, we investigated the possibility that PTH-related protein (PTHrP), which is produced in lactating mammary glands, is a putative calciotropic factor acting systemically during lactation. To test this hypothesis, we examined changes in urinary phosphate and cAMP excretion in relation to suckling since phosphaturia (P-uria) and increased urinary cAMP excretion are sensitive parameters of PTHrP action on the kidney. When lactating rats (separated from their pups overnight) were allowed to suckle pups for 1 h, they showed a marked P-uria which lasted 3-4 h. In most instances, a transient increase in cAMP excretion preceded the P-uria. These effects were not abolished by thyroparathyroidectomy; hence they are not attributable to a transient increase in PTH secretion. Administration of PRL or oxytocin did not induce significant P-uria. When lactating rats were pretreated with anti-PTHrP anti-serum, the suckling-associated P-uria was prolonged and augmented. This prolongation of P-uria was similar to the effects observed when exogenous PTHrP (1-34)amide was administered in the presence of the antiserum. These data support the hypothesis that some of the PTHrP produced in lactating mammary glands may be released systemically during suckling and act in an endocrine manner on target organs such as the kidney.

Animals↗
PubMed1990

Modifications of position 12 in parathyroid hormone and parathyroid hormone related protein: toward the design of highly potent antagonists.

Truncated N-terminal fragments of parathyroid hormone (PTH), [Tyr34]bovine PTH(7-34)NH2, and parathyroid hormone related protein (PTHrP), PTHrP(7-34)NH2, inhibit [Nle8,18,[125I]iodo-Tyr34]-bPTH(1-34)NH2 binding and PTH-stimulated adenylate cyclase in bone and kidney assays. However, the receptor interactions of these peptides are 2-3 orders of magnitude weaker than those of their agonist counterparts. To produce an antagonist with increased receptor-binding affinity but lacking agonist-like properties, structure-function studies were undertaken. Glycine at position 12 (present in all homologues of PTH and in PTHrP), which is predicted in both hormones to participate in a beta-turn, was examined by substituting conformational reporters, such as D- or L-Ala, Pro, and alpha-aminoisobutyric acid (Aib), in both agonist and antagonist analogues. Except for N-substituted amino acids, which substantially diminished potency, substitutions were well tolerated, indicating that this site can accept a wide latitude of modifications. To augment receptor avidity, hydrophobic residues compatible with helical secondary structure were introduced. Incorporation of the nonnatural amino acids D-Trp, D-alpha-naphthylalanine (D-alpha-Nal), or D-beta-Nal into either [Tyr34]bPTH(7-34)NH2 or [Nle8,18,Tyr34]bPTH(7-34)NH2 resulted in antagonists that were about 10-fold more active than their respective 7-34 parent compound. Similarly, [D-Trp12]PTHrP(7-34)NH2 was 6 times more potent than the unsubstituted peptide but retained partial agonistic properties, although markedly reduced, similar to PTHrP(7-34)NH2. The antagonistic potentiating effect was configurationally specific.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1990

Extramucosal spread and development of hepatitis in immunodeficient and normal mice infected with rhesus rotavirus.

The pathogenic profiles of two heterologous animal rotaviruses, rhesus rotavirus strain MMU 18006 and bovine rotavirus strain WC3, were evaluated in mice with severe combined immunodeficiency (SCID mice) and normal BALB/c mice. Control animals were inoculated with homologous murine strain EDIM 5099 or a tissue culture-adapted murine rotavirus. Heterologous infection with rhesus rotavirus resulted in hepatitis in 84% of SCID and 21% of BALB/c mice, with mortality rates of 27 and 0%, respectively. Surviving SCID animals developed chronic liver disease, while symptoms in BALB/c mice resolved in 2 to 4 weeks after onset. Histopathologic examination revealed a diffuse hepatitis with focal areas of parenchymal necrosis. Rotavirus was detected in liver tissue from 100% of 29 SCID and 85% (11 of 13) BALB/c animals tested by cell culture infectivity, immunofluorescence, or electron microscopy. No extramucosal spread of virus or hepatitis was observed after infection with heterologous bovine strain WC3 or homologous murine rotaviruses. This finding of a novel rotavirus-induced disease manifestation suggests altered tissue tropism in a heterologous host for a group of viruses previously shown to replicate exclusively in the gut mucosa. The implications of our observations suggest that in human vaccine trials utilizing heterologous rotavirus strains, special attention should be paid to children with immunodeficiency disorders, and screening for hepatic function should be included in vaccine protocols.

Animals↗
PubMed1990

Effect of rotavirus infection and malnutrition on uptake of a dietary antigen in the intestine.

Intestinal absorption of ovalbumin (OVA), a dietary macromolecule, was studied in malnourished and normally nourished suckling mice after experimentally induced infection with rotavirus. All mice developed diarrhea within 24 to 48 h postinoculation. The malnourished animals exhibited more severe symptoms and an increased number of rotavirus-containing enterocytes in intestinal sections as compared to well-nourished mice when examined 3 d postinoculation, at the peak of diarrhea. Histopathologic examination revealed villus atrophy and pronounced vacuolization of villus enterocytes in association with malnutrition and rotavirus infection. The combination of malnutrition and viral infection resulted in more severe mucosal damage, including disruption of microvillus borders. After a single oral dose of 100 micrograms OVA at 3 d postinoculation, the concentration of OVA in serum, gastric content, intestinal lavage fluid, and intestinal tissue homogenates was measured at different time intervals. The concentrations of OVA in intestinal tissue were significantly higher in malnourished animals, whereas lower values were found in rotavirus-infected animals. In all mice, OVA was rapidly absorbed and could be consistently detected in the serum within 5 min. OVA levels peaked at 45 to 60 min and then gradually declined. In malnourished infected animals, the uptake of OVA was rapid and resulted in significantly higher serum levels when compared to well nourished or uninfected controls, respectively. The peak uptake of OVA per g body wt was about 4.5 times more in malnourished infected compared to well-nourished infected mice and 2.5 times higher in normally nourished infected animals when compared to uninfected controls. These results indicate that rotavirus infection in association with malnutrition may cause a significant rise in gut permeability to environmental macromolecules.

Animals↗
PubMed1990

The bovine renal parathyroid hormone (PTH) receptor has equal affinity for two different amino acid sequences: the receptor binding domains of PTH and PTH-related protein are located within the 14-34 region.

Previous studies examining the interaction of PTH and PTH-related protein (PTHrP) with target tissue have for the most part emphasized the similarity between the two hormones in binding to and activating receptors. This observation that two peptides with limited homology have equal affinities for the same receptor is unusual. In this report we investigated two aspects of PTH/PTHrP-receptor interactions. First, the nonhomologous 14-34 regions of PTH and PTHrP were synthesized and evaluated. Second, hybrid peptides containing the 7-18 fragment of one hormone combined with the 19-34 region of the other hormone were studied to determine whether interactions between these two regions are required for receptor recognition. All four peptides were examined in bovine renal cortical membrane and rat osteosarcoma (ROS 17/2.8) cell PTH-binding and PTH-stimulated adenylate cyclase assays. The results indicate that the receptor-binding domains of PTH and PTHrP lie outside of the 1-13 region, the region containing sequence homology shared by the two hormones, and that two peptides of different amino acid sequence bind with equal affinity to the bovine renal PTH receptor. However, in the absence of the N-terminal region, the rat bone PTH receptor displays a preference for the C-terminal (19-34 sequence) region of PTHrP.

Adenylyl Cyclases↗
PubMed1989

The sz mutant hamster: a genetic model of epilepsy or of paroxysmal dystonia?

Attacks of sustained dystonic postures of limbs and trunk can be initiated by mild environmental stimuli in an inbred line of Syrian hamsters. The trait is determined by an autosomal simple recessive genetic mutation, originally designated by the gene symbol sz, because the abnormal movements were thought to represent epileptic seizures. The attacks, which can be reproducibly initiated by placing the sz mutant hamsters in a new environment, begin with rapid twitches of the vibrissae, flattened ears, and flattened posture of the trunk while walking, followed by facial contortions, rearing, and sustained posturing of trunk and limbs, often resulting in falling over to the side or backwards. In the final stage, the hamsters became immobile, which can last for hours. An increased tone of limbs and trunk muscles can be palpated during the attack. Electromyographical recordings in awake, unrestrained mutant hamsters showed that the onset of the attack coincided with continuous tonic muscle activity and phasic bursts, which were present even when the animals did not move. During the attack, the animals continue to react to external stimuli. Bilateral electroencephalographic (EEG) recordings before and during motor disturbances in sz mutant hamsters showed no abnormalities. The severity of the dystonic syndrome in hamsters is age dependent with a peak at about 30-40 days of age. A score system for grading type and severity of dystonic attack was developed for use in drug activity studies. The severity of the attack was reduced or attacks were completely prevented by diazepam (1-2.5 mg/kg i.p.) and valproic acid (100-400 mg/kg i.p.) in a dose-dependent fashion. The latency to dystonic movements was significantly increased by diazepam but markedly reduced by subconvulsive doses of pentylenetetrazol (40 mg/kg s.c.). Diazepam antagonized the latency-reducing action of pentylenetetrazol in the hamsters. The pathophysiology and pharmacological sensitivity of the dystonic attacks in these animals remain to be further clarified, but the data indicate that the sz mutant hamsters might represent an interesting genetic model for paroxysmal dystonia. In view of these data, we propose that the hamster mutation should be re-named dystonic and that the new gene symbol should be designated dtsz.

Animals↗
PubMed1989

Immune consequences of nonoperative treatment of splenic trauma in the rat model.

To investigate the immunologic consequences of non-operative management of splenic injury, three parameters were studied: survival following pneumococcal sepsis, clearance of blood-borne bacteria, following Hemophilus influenzae challenge, and antibody response to type III pneumococcal capsular polysaccharide. Two hundred twenty-five Sprague-Dawley rats were divided into three groups and subjected either to a splenectomy, a sham operation, or standard blunt trauma. A significant increase in mortality was noted in the splenectomized group as compared with both the traumatized and control groups when challenged with Streptococcus pneumoniae. In both the control and trauma groups, H influenzae cleared significantly within 18 hours. Blood-borne bacteria persisted at the same level for 72 hours in the splenectomized animals. Four and 11 days later, the antibody level in both traumatized and control groups was higher than in the splenectomized subjects (P less than .001). There was no difference in the serum antibody level between the control and trauma groups at four days. However, at 11 days the trauma group showed a significant decrease in the antibody level (P less than .05). It can be concluded that following spontaneously-healing splenic trauma in the rat model, survival, bacterial clearance, and antibody response were all superior to that observed in the splenectomized subjects. In addition, the healed splenic disruption did not impair clearance of blood-borne encapsulated bacteria.

Animals↗
PubMed1989

Valproic acid in amygdala-kindled rats: alterations in anticonvulsant efficacy, adverse effects and drug and metabolite levels in various brain regions during chronic treatment.

Amygdala-kindled rats were treated with valproic acid (VPA; administered as its sodium salt) 3 times daily at 200 mg/kg i.p. for 6 weeks, and anticonvulsant and adverse effects during this period were studied. Groups of nonkindled rats were treated in parallel for determination of VPA and its major active metabolites in various brain regions after different durations of treatment. After the first injection of VPA, 200 mg/kg, seizure severity, seizure duration and duration of electrical afterdischarges recorded from the stimulated amygdala were reduced significantly, but only one of nine animals was protected completely from kindled seizures. At day 3 of chronic treatment, the anticonvulsant activity of VPA had increased markedly so that seven of nine animals were totally protected from seizures. However, this potent anticonvulsant effect was only transitory so that after 1 week of treatment the anticonvulsant effect of the medication was similar to that obtained after the first dosing. The effect of VPA remained at this level for the subsequent weeks, but there was a second, more permanent increase in the number of protected animals after 4 to 6 weeks. Plasma and brain levels of VPA and its metabolites remained relatively constant throughout the chronic treatment although there was a moderate accumulation of some metabolites, e.g., trans isomer of 2-propyl-2-pentenoic acid, in specific brain nuclei. The most prominent adverse effects of VPA were ataxia, muscle relaxation, wet-dog shake behavior and an increase in body temperature. Except for body temperature, tolerance developed to these adverse effects, but escape from wet-dog shake behavior occurred much more rapidly than reduction of other adverse effects. Pathohistological examination of liver sections from animals treated with VPA for 6 weeks showed no indication of any hepatotoxic effects. After drug withdrawal, kindled seizure parameters returned toward control values without evidence of significant carry-over effects. Five days after termination of treatment, only minute amounts of VPA and trans isomer of 2-propyl-2-pentenoic acid were determined in some brain regions, indicating that there was no persistence of active drug or metabolite concentrations in the brain.

Amygdala↗
PubMed1988

Marked increase in anticonvulsant activity but decrease in wet-dog shake behaviour during short-term treatment of amygdala-kindled rats with valproic acid.

The anticonvulsant activity of valproic acid (VPA) was determined in amygdala-kindled rats after single and repeated (total of 7 injections given 3 times per day) administration of 200 mg/kg i.p. After a single injection, VPA significantly reduced the severity and duration of the kindled seizures and decreased the duration of after-discharges recorded from the stimulated amygdala, but only 12% of the animals were totally protected from seizures. The percentage of animals totally protected increased to 88% after 7 doses. This pronounced increase in the anticonvulsant activity was not related to alterations in the plasma concentrations of VPA or its major active metabolites. Furthermore, determination of VPA and its metabolites in the substantia nigra after a single and repeated administration yielded the same data, again indicating that the increase in the anticonvulsant activity was not due to drug accumulation. In contrast to the marked increase in the anticonvulsant efficacy of VPA during short-term treatment, wet-dog shake behaviour induced by a single injection of the drug was significantly attenuated after repeated dosing, indicating that the anticonvulsant effect of VPA and the wet-dog shake behaviour induced by the drug were not mediated by the same mechanism. This was substantiated by experiments with one of the major metabolites of VPA in rat plasma, trans-2-en-VPA, which had approximately the same anticonvulsant efficacy as VPA but did not induce wet-dog shakes in rats.

Amygdala↗
PubMed1988

Direct action of the parathyroid hormone-like human hypercalcemic factor on bone.

Peptides containing residues 1-34 of the human parathyroid hormone (PTH)-like hypercalcemic factor (hHCF), termed hHCF-(1-34)-NH2, produce effects similar to those of PTH in several biological systems in vitro and in vivo. However, there is conflicting evidence regarding the potency of hHCF on bone and, by implication, its role in calcium mobilization and the skeletal contribution to tumor-associated hypercalcemia. To resolve this conflict, the effects of infusing either hHCF-(1-34)-NH2 or a peptide containing residues 1-34 of bovine PTH [bPTH-(1-34)] into unrestrained thyroparathyroidectomized rats on a low calcium diet were compared. Direct effects on bone histology and serum calcium levels, which are totally dependent on calcium mobilization from bone in these animals, were examined. bPTH-(1-34) and hHCF-(1-34)-NH2 were equipotent in producing dose-dependent calcium mobilization from bone. At an infusion rate of 0.1 nmol/hr, both peptides produced hypercalcemia and extensive nephrocalcinosis. Histomorphometric analysis of tibiae from these animals after 48 hr of peptide infusion showed a dose-related increase in osteoclast number from 3-5 cells per mm2 at 0.01 nmol/hr to approximately equal to 32 cells per mm2 at 0.1 nmol/hr of hHCF or bovine PTH. These findings indicate that hHCF has a direct PTH-like effect on bone and, in this model system, the hHCF-(1-34)-NH2 is equipotent to bPTH-(1-34).

Animals↗
PubMed1988

The effects of teaching experience on levels of alienation.

This study was designed to measure the levels of alienation among American student and full-time teachers, based on the length of their experience with the public school organization. One hundred seventy eight subjects, including 113 full-time teachers and 65 student teachers, were administered the Dean Alienation Scale. Analysis of the data indicated that student teachers had significantly higher levels of alienation, isolation, normlessness, and powerlessness, than did full-time teachers. The less experience the teacher had, the higher were his or her levels of total alienation and powerlessness.

Female↗