Biomedical subjects

L A Kerr

Publications and source records attributed to L A Kerr.

At least 19 recordsLinked to original sources

PubMed2001

Atypical rumen acidosis in a dairy herd from whiskey distillery by-products.

Decreased milk and reproductive performance, high incidence of gastrointestinal surgeries, and acute deaths were investigated in a herd of Holstein cows. The health problems were due to abnormally low rumen pH's from ingestion of 30 gal/hd/d of a 3.4 pH liquid feed ingredient. A combination of acid neutralizing agents (calcium hydroxide plus sodium carbonate) alleviated the toxic effects of the feed ingredient.

Acidosis↗

PubMed2000

Duplicate sampling reproducibility of atmospheric residues of herbicides for paired pan and high-volume air samplers.

The reproducibility of collection of atmospheric residues of the herbicides 2,4-D and triallate as bulk (wet plus dry) deposition samples by paired pan samplers and as particulate (filter) and vapour (PUF/XAD-2 resin cartridge) samples by paired high-volume air samplers was determined. Variability of herbicide concentrations in paired bulk deposition samples was within 25% for 65 and 80% of the samples for 2,4-D and triallate, respectively, with approximately 90% of the paired samples being within a factor of 2 for both herbicides. The vapour samples of 2,4-D and triallate showed similar reproducibilities. The highest reproducibility was observed for the filter samples with 92% of the paired data sets for 2,4-D being within 25% variability. No triallate was detected in the filter samples.

2,4-Dichlorophenoxyacetic Acid↗

PubMed2000

Fatal Clostridium botulinum toxicosis in eleven Holstein cattle fed round bale barley haylage.

Twenty-two lactating Holstein cattle in Tennessee had clinical signs of intoxication with preformed Clostridium botulinum toxin. These signs included weakness, paralysis of the tongue and chest muscles, abdominal breathing, and, in 11 of the 22 cows, death. Differential diagnoses included hypocalcemia, hypomagnesemia, carbohydrate overload, and several toxicoses including mycotoxin, lead, nitrate, organophosphate, atropine or atropine-like alkaloid, and botulism. A diagnosis of botulism by the ingestion of preformed C. botulinum type B toxin was made by eliminating these other diseases, by finding C. botulinum type B spores in 3 bales of round bale barley haylage fed to these cattle, and by isolating preformed type B toxin from 1 of the 3 bales. Confirmation of the toxin type was made by demonstrating mouse lethality by intraperitoneal injection of specimen extracts with neutralization by C. botulinum type B antitoxin. The haylage, harvested green and encased in black plastic bags to facilitate fermentation, was presumably contaminated by the botulinum toxin when fermentation failed to produce enough acid to lower the pH to 4.5, the pH below which C. botulinum growth is inhibited. Farmers and ranchers who use round hay balers to produce haylage should be alert to this potential problem.

Animal Feed↗

PubMed2000

Overactive bladder significantly affects quality of life.

Overactive bladder (OAB), with symptoms of frequency, urgency, and urge incontinence, substantially affects the lives of millions of people. The symptoms associated with OAB can significantly affect the social, psychological, occupational, domestic, physical, and sexual aspects of those who suffer from it. Unfortunately, many sufferers are reluctant to discuss their condition with their healthcare provider or family members. As a result, OAB remains underreported, despite increased awareness and improved diagnosis and treatment. Health-related quality of life can be measured objectively, and several instruments have been developed, validated, and used in research. Currently, there are 2 major types of quality-of-life questionnaires: generic and disease specific. Although these questionnaires have been helpful and are widely used, the goal is to establish a single questionnaire that is acceptable throughout the world for use by urologists, gynecologists, urogynecologists, geriatricians, and epidemiologists.

Adult↗

PubMed1999

Fatal privet (Ligustrum amurease) toxicosis in Tennessee cows.

Five of 24 cows pastured in a 40-acre field in east Tennessee died after they consumed leaves from a privet (Ligustrum amurease) hedge. Clinical findings included ataxia, recumbency with an inability to stand, depression, greenish nasal discharge, cessation of rumination, normal body temperature, and increased heart and respiratory rates. Differential diagnoses included grass tetany, nitrate toxicosis, and plant toxicosis. Privet toxicosis was confirmed by finding privet in ruminal contents, by the presence of a large quantity of privet in the field, by observing places where this privet had been eaten by the cows, by the immediate cessation of the problem when the cows were removed from the field, and by observing no recurrent problems after the privet was destroyed with a herbicide and the cows were returned to the field.

Animals↗

PubMed1999

Rel/NF-kappaB represses bcl-2 transcription in pro-B lymphocytes.

The mechanisms controlling programmed cell death (PCD) during early B cell development are not well understood. Members of both the Bcl-2 family of apoptosis-related proteins and the nuclear factor-kappa B/Rel (NF-kappaB/Rel) family of transcription factors are expressed differentially during B cell development. To date, however, no direct interactions between these two families have been demonstrated. The FL5.12 cell line represents a model for progenitor B cell development. Such cells reproducibly undergo PCD upon IL-3 withdrawal. The signal to enter the apoptotic pathway is mediated by a shift in the ratio of Bcl-2:Bax. While bax levels remain constant, bcl-2 transcription rate, steady-state mRNA, and protein levels decrease. Analysis of the bcl-2 promoter reveals 3 kappaB sites functionally able to bind kappaB factors from FL5.12 nuclear extracts. Cotransfection studies demonstrate that NF-kappaB factors can repress bcl-2 transcription and that site-directed mutagenesis of the kappaB motifs abolishes this repression. These studies suggest that NF-kappaB mediates PCD in pro-B cells through transcriptional repression of the survival gene bcl-2, thus shifting the bcl-2:bax ratio in favor of death-promoting complexes.

Animals↗

PubMed1998

Malignant osteoclast-like giant cell tumor of the kidney.

Osteoclast-like giant cell tumors are rare mesenchymal tumors that typically present in osseous tissue and are remarkable because of their slow growth. We report the sixth documented case of a malignant osteoclast-like giant-cell tumor primary to the kidney of an 81-year-old man with a 5-month history of hematuria. Postnephrectomy analysis of the tumor, including immunohistochemical stains and electron microscopy, confirmed the diagnosis. Although the patient died of unrelated complications, metastatic disease was suspected.

Aged↗

PubMed1998

Pigweed (Amaranthus retroflexus) toxicosis in cattle.

Four of approximately 15 dry cows introduced on a 10-acre fescue-clover-orchard grass-Dallis grass pasture in East Tennessee became recumbent. Clinical findings included depression, muscle tremors, increased heart and respiratory rates, hypocalcemia, hypomagnesemia, hyperkalemia, azotemia, and elevated creatinine phosphokinase. Three cows recovered; 1 died. Differential diagnoses considered were hypocalcemia, hypomagnesemia, rabies and toxicoses from Amaranthus retroflexus (pigweed), Quercus spp (oak), Cassia spp (senna) oxalate (Aspergillus niger or flavus), mycotoxicosis, lead, arsenic or insecticides. Pigweed toxicosis was confirmed based on clinical and postmortem findings, partially ingested pigweed in the pasture, and ruling out other possible causes. Several factors probably contributed to this incident: since the cattle were newly introduced to the pasture, the cattle may have been attracted to the pigweed in the new pasture and became addicted to it; their rumen microflora had little time to acclimate to the pigweed; and dry weather produced poor forage quality thus forcing the cows to eat the pigweed.

Animals↗

PubMed1997

Acute toxicosis in cattle sprayed with endosulfan.

Two cattle died acutely after being sprayed for lice control with a cyclodiene organochlorine insecticide, endosulfan, not labelled for use in cattle. Three other cattle became acutely ill, but survived after symptomatic therapy and removal of the insecticide from their skin and prevention of enterohepatic circulation. These cases illustrated the risk of acute toxicosis when organochlorine insecticides are used off-label and the potential for illegal tissue and milk residues.

Acute Disease↗

PubMed1996

The TAP complex influences allorecognition of class II MHC molecules.

The influence of the TAP complex on T-cell allorecognition of MHC class II molecules was examined using human B-cell lines that have mutations in the TAP 1 or 2 genes. The TAP mutations led to the loss of allorecognition for two of 28 anti- HLA-DR T-cell clones. Restoration of TAP expression by transfection of a TAP 2 cDNA clone led to recovery of the alloresponse for both clones. These results could be explained in two ways. First, TAP dependence could reflect specificity for a peptide derived from an MHC class I molecule that is less efficiently generated by the endocytic pathway in the TAP-deficient stimulator cells owing to reduction in surface class I expression. The proliferative responses of these clones to the TAP-deficient stimulator cells was not restored by rescue of cell-surface expression of class I molecules by low temperature culture or by the addition of class I-binding peptides. These data therefore favor the alternative explanation that class II loading by some peptides is TAP dependent. Circumstances that lead to the amplification of this minority pathway of endogenous presentation by class II MHC molecules may have the potential to interrupt self-tolerance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1994

Tumor localization and therapeutic potential of an antitumor-anti-CD3 heteroconjugate antibody in human renal cell carcinoma xenograft models.

A heteroconjugate (HC) antibody, constructed with the monoclonal antibody (MoAB) Dal K29 to human renal cell carcinoma (RCC) and an anti-CD3 MoAb, could induce a very high level of lysis of human RCC cells when incubated with human peripheral blood lymphocytes (PBL) in vitro (Kerr et al., 1990, J. Immunol., 144, 4060-4067). We now report that this HC antibody selectively localizes in RCC xenografts in nude mice and could inhibit RCC in an ascites tumor xenograft model when administered intraperitoneally together with PBL.

Animals↗

PubMed1994

Abnormal detrusor function precipitating hydronephrosis identified by extended voiding cystometry.

Extended voiding cystometry was performed to elucidate the true detrusor function in a patient originally misdiagnosed during standard fill cystometry. This methodology allows for observation of an extended period of bladder activity and eliminates the artifacts of classical fill cystometry, which are detrusor instability and noncompliance. A chronically elevated intravesical pressure between contractions (inter-contraction pressure) representing high pressure residual urine, as well as frequent, high amplitude, long duration detrusor contractions during the storage phase and a large post-void residual urine volume were documented. These urodynamic abnormalities are known to precipitate hydroureteronephrosis in the absence of vesicoureteral reflux.

Adult↗

PubMed1994

Radical retropubic prostatectomy for prostate cancer in the elderly and the young: complications and prognosis.

The young and the elderly patients with surgically resectable prostate cancer require considerations unique to their age group. From 1966 to 1988, 191 patients who were < or = 55 years old and 51 elderly patients who were > or = 75 years old underwent radical retropubic prostatectomy. Compared with younger patients, elderly patients had a higher pathologic stage (71 versus 45% stage pT3 or greater, p < 0.001) and higher-grade lesions (49 versus 21%, p < 0.001). Survival was significantly worse compared with age-matched controls for younger patients with high-stage or high-grade lesions (p < 0.001). No elderly patients died within the first 5 years after hospital dismissal. Two thirds of elderly as well as younger patients had no perioperative complications. Significant urinary incontinence occurred in 16% of the elderly compared with 3% of the younger patients (p = 0.001) at 1 year. These data reflect our philosophy of using surgical treatment for patients with unfavorable, large-volume disease even when patients are elderly; if well-selected, these patients can have excellent survival. The observed higher incontinence rate in the elderly should be part of the discussion with the patient before operation.

Adenocarcinoma↗

PubMed1993

The major histocompatibility complex-encoded proteasome component LMP7: alternative first exons and post-translational processing.

The LMP7 gene maps to the major histocompatibility complex class II region. The derived protein sequence shares homology with N-terminal amino acid sequence from proteasome subunits (Glynne, R., Powis, S. H., Beck, S., Kelly, A., Kerr, L.-A. and Trowsdale, J., Nature 1991. 353: 357) and it has been suggested that LMP7 is involved in the degradation of endogenous antigens prior to their presentation through class I (Robertson, M., Nature 1991. 353: 300). We have isolated a second LMP7 transcript which has a different first exon to the published sequence. Both transcripts were expressed in cell lines from a number of tissues and both responded to interferon-gamma. An anti-LMP7 antiserum precipitated proteins similar in their migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis to those precipitated by an anti-proteasome serum. Western blot analysis of anti-proteasome precipitates demonstrated that the LMP7 protein is incorporated into the proteasome but has a molecular mass of 23 kDa, 7 kDa smaller than expected fro the derived protein sequence of either of the cDNA. A pulse-chase experiment indicated that post-translational cleavage of the LMP7 N terminus precedes the formation of the 23-kDa proteasome subunit. To our knowledge, LMP7 provides the first biochemical evidence for such processing of proteasome components.

Alternative Splicing↗

PubMed1993

Renal angiomyolipoma in association with pulmonary lymphangioleiomyomatosis: forme fruste of tuberous sclerosis?

From 1976 to 1989, 27 patients with pulmonary lymphangioleiomyomatosis were seen at our institution. Twenty-five had no signs or symptoms of tuberous sclerosis; 21 of these had abdominal imaging or surgical exploration to make the diagnosis of renal angiomyolipoma in seven patients, all female. Three presented with symptoms secondary to renal disease, three with pulmonary manifestations, and one with both. Renal disease was bilateral in four patients; four patients underwent nephrectomy and two tumors were embolized. All patients experienced spontaneous pneumothoraces during the course of their disease. There was one respiratory death. It is our belief that any patient presenting with angiomyolipoma and a history of pulmonary problems should be evaluated for pulmonary lymphangioleiomyomatosis with a limited computed tomography scan of the chest at the time of abdominal imaging. The surgical treatment of angiomyolipoma when associated with lymphangioleiomyomatosis is predicated on the ability to adequately manage the complicating lung disease perioperatively.

Adult↗

PubMed1992

Polymorphism in a second ABC transporter gene located within the class II region of the human major histocompatibility complex.

Recent studies have identified genes within the major histocompatibility complex (MHC) that may play a role in presentation of antigenic peptides to T cells. We have previously described RING4, a gene within the human MHC class II region that has sequence homology with members of the ABC ("ATP-binding cassette") transporter superfamily. We now report the nucleotide sequence of RING11, a second ABC transporter gene located approximately 7 kilobases telomeric to RING4, RING11 is gamma-interferon inducible, a property shared with other genes involved in antigen presentation. Comparison between the amino acid sequences of RING11 and RING4 reveals strong homology. We propose that they form a heterodimer that transports peptides from the cytoplasm into the endoplasmic reticulum. We have identified two RING11 alleles, which differ in the length of their derived protein sequence by 17 amino acids. The more common of these alleles is present in a Caucasoid population at a frequency of 79%.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

Assembly and function of the two ABC transporter proteins encoded in the human major histocompatibility complex.

Presentation of cytoplasmic antigens to class I-restricted cytotoxic T cells implied the existence of a specialized peptide transporter. For most class I heavy chains, association with peptides of the appropriate length is required for stable assembly with beta 2-microglobulin. Mutant cells RMA-S and .174/T2 neither assemble stable class I molecules nor present intracellular antigens, and we have suggested that they have lost a function required for the transport of short peptides from the cytosol to the endoplasmic reticulum. The genetic defect in .174 has been localized to a large deletion in the class II region of the major histocompatibility complex, within which two genes (RING4 and RING11) have been identified that code for 'ABC' (ATP-binding cassette) transporters. We report here that the protein products of these two genes assemble to form a complex. Defects in either protein result in the formation of unstable class I molecules and loss of presentation of intracellular antigens. The molecular defect in a new mutant, BM36.1, is shown to be in the ATP-binding domain of the RING11/PSF2 protein. This is in contrast to the mutant .134, which lacks the RING4/PSF1 protein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

Suspected buttercup (Ranunculus bulbosus) toxicosis with secondary photosensitization in a Charolais heifer.

A presumptive diagnosis of buttercup toxicosis with photosensitization secondary to hepatotoxicity was made in an 18-mo-old Charolais heifer. The differential diagnosis included salmonellosis, aflatoxicosis, bovine virus diarrhea, internal parasite infestation, and plant toxicosis with either primary or secondary photosensitization. All these possibilities were excluded except buttercup toxicosis with photosensitization secondary to hepatotoxicity. While this diagnosis was not absolutely confirmed, it was the most likely cause of the disease and raised the intriguing possibility that protoanemonin, buttercup's toxic principle, is hepatotoxic.

Animals↗