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Biomedical subjects

J E Kennedy

Publications and source records attributed to J E Kennedy.

At least 19 recordsLinked to original sources

Identification of novel alternatively spliced isoforms of the tropomyosin-encoding gene, TMnm, in the rat cochlea.

Analysis of a rat cochlear cDNA library for the expression of the non-muscle (nm) tropomyosin (TM)-encoding gene (TMnm), demonstrated that four nm isoforms were present. These four TMnm variants are NM-1, NM-2, NM-3 and NM-4. Nucleotide (nt) sequencing revealed that all these isoforms expressed the nm exon 1b sequence, but varied in their usage of the alternatively spliced exons 6a and b and 9a/b and d, representing skeletal muscle (sk) (exons 6b and 9a/b) and nm (6a and 9d) sequences. A novel exon 9 (designated as exon 9c) was associated with the NM-4 isoform and was also found to be expressed in the cochlea. Comparisons of the nt and amino acid (aa) sequences demonstrated a high homology between rat, mouse and human sequences encoding the 'classical' nm isoform, TM30nm, which is designated herein as NM-1. The rat NM-1 nt homology with mouse and human sequences also included the 3' untranslated region. Homologies were found between aa sequences of the C termini of NM-1 and the TM alpha smooth muscle and TM beta nm isoforms, between the sk sequence of NM-3 and the TM alpha and beta sk isoforms, and between the novel 9c sequence of NM-4 and the TM alpha brain-1 isoform. These data predict that the nm isoforms share biochemical properties described for the other TM isoforms.

Alternative Splicing

Intraoperative consultation of ovarian neoplasms.

A review of 313 intraoperative consultations and/or frozen section evaluations of neoplasms of the ovary was conducted. The intraoperative diagnosis of benign or malignant was compared with the diagnosis found at permanent section. Only six cases were deferred to permanent section. The overall accuracy was 93.9%. The sensitivity was 72.7%, and this was explained by the high proportion of borderline or low malignant cell tumors in this series. The specificity and predictive values were in excess of 95%. Thirteen cases were diagnosed incorrectly at intraoperative consultation. Eight of these were judged to be sampling errors, one was due to poor technical quality, and four were attributed to interpretation errors. Intraoperative consultation is, and should continue to be, a valuable tool in the evaluation of ovarian neoplasms.

Diagnostic Errors

Platelet-derived growth factor and dexamethasone combined with a collagen matrix induce regeneration of the periodontium in monkeys.

Platelet-derived growth factor (PDGF) and the glucocorticoid dexamethasone combined with a collagen carrier matrix (CM) induced regeneration of the periodontium in monkeys. Regeneration was stringently defined as: (1) new cementum, (2) new supra-crestal bone extending coronally from the residual alveolar interdental septum and (3) functionally-oriented periodontal ligament fibers attaching new cementum to new bone. A single application of PDGF/dexamethasone/CM or CM was placed in debrided lesions of experimental periodontitis displaying 3-5 mm of attachment loss associated with horizontal and angular bony defects. Regeneration, judged histologically by these criteria and quantified by computer assisted histomorphometry after 4 weeks, was present only in PDGF/dexamethasone/CM treated lesions and not in those treated with CM or debridement alone. PDGF/dexamethasone/CM induced 5-fold more new cementum and ligament, and 7-fold more supra-crestal bone than control treatments. The presence of substantial amounts of regenerated periodontium including increased height of the alveolar bone; fill of vertically resorbed interdental alveolar septa in PDGF/dexamethasone/CM treated lesions suggests that this combination may provide a new therapeutic agent for the regeneration of lesions of periodontitis associated with horizontal as well as angular bony defects.

Alveolar Process

The value of endocervical curettage at time of cervical cone biopsy.

Two hundred eighty-nine patients were evaluated over a 23-month period to assess the efficacy of postcone biopsy endocervical curettage at the time of cervical conization. One hundred eleven patients were excluded because the endocervical curettage was insufficient or not performed, the final pathology on the cone biopsy and endocervical curettage revealed no dysplasia or cancerous process, or the endocervical margins were not assessed, leaving a total of 178 patients in the study population. A negative conization endocervical margin virtually assures no disease in the upper endocervical canal. The negative predictive value in this study population was 97%. We conclude that routine endocervical curettage is unnecessary for most patients and should be primarily considered for patients who are postmenopausal or for those receiving suboptimal conizations.

Adolescent

Characterization of the allelic differences in the mouse cardiac alpha-myosin heavy chain coding sequence.

We have obtained and sequenced the coding sequence of the mouse cardiac alpha-myosin heavy chain (Myhc alpha) from the A/J, BALB/cByJ, C57BL/6J, and DBA/2J inbred mouse strains. Overlapping cDNA sequences were obtained using RNA-PCR and anchor-PCR techniques for these studies. In the A/J mouse strain, the full-length message is 5989 bp long and encodes for a protein consisting of 1938 amino acids (Mr 223,689). The protein deduced sequence of the A/J Myhc alpha was compared with corresponding sequences of human and rat Myhc alpha and beta. These results demonstrated that the mouse Myhc alpha is highly conserved and has maintained the alpha-isoform-specific divergent cluster observed in other Myhc alpha proteins. One difference was the loss of a glutamine at residue 1932, which is due to a change in an RNA splicing site sequence. Allelic variability was observed in both nucleotide and amino acid sequences among the four different inbred mouse strains and generally appears to be random in nature. Three of the nucleotide changes resulted in a different amino acid, while the remaining 46 were silent substitutions.

Alleles

Platelet-derived and insulin-like growth factors stimulate regeneration of periodontal attachment in monkeys.

Regeneration of cementum, ligament, bone and new attachment was achieved by introducing mixtures of recombinant human platelet-derived growth factor and insulin-like growth factor into debrided lesions of experimentally induced periodontitis in monkeys. This growth factor therapeutic regimen induced the regeneration of nearly 50% of the lost attachment within 4 weeks. New attachment in some cases included regeneration of horizontally resorbed interdental septa. These observations suggest that predictable, clinically significant gains in new attachment may be possible through the use of highly purified human recombinant growth factors delivered to debrided lesions of adult periodontitis in appropriate, inert carrier vehicles.

Alveolar Bone Loss

DNA analysis of atrial myxomas.

The atrial myxoma is a primary tumor of the heart which may have an uncertain clinical course. In this study, we performed flow cytometric DNA analysis of 15 paraffin-embedded atrial myxomas and correlated DNA ploidy status and proliferative fraction with clinical findings. Twelve of 15 cases (80 percent) were diploid and the remaining three cases (20 percent) were aneuploid. Two patients with aneuploid histograms were free of tumor at the time follow-up; the third patient experienced local tumor recurrence and metastases. Five patients with diploid myxomas demonstrated an elevated (greater than or equal to 17 percent) proliferative cell cycle fraction; four of these patients experienced embolic phenomenon or tumor recurrence. This pilot study suggests that an atrial myxoma with either aneuploid DNA content or elevated proliferative fraction may be associated with aggressive biologic behavior.

Aneuploidy

Monitoring bovine viral diarrhea virus vaccines for adventitious virus, using T1 ribonuclease viral RNA oligonucleotide fingerprinting.

Viral RNA oligonucleotide fingerprinting was used to discriminate 3 cytopathic vaccine bovine viral diarrhea viruses (BVDV) grown in medium supplemented with serum contaminated with noncytopathic BVDV from the same 3 viruses grown in cell culture free of BVDV. Oligonucleotide fingerprinting also effectively discriminated between reference Singer BVDV, NADL BVDV, and New York-1 BVDV grown in BVDV-free noncontaminated or BVDV-contaminated cell cultures. Oligonucleotide fingerprint mapping of viral RNA maybe used to determine the purity of virus stocks, as well as that of BVDV vaccines.

Animals

Investigation of bovine viral diarrhea virus infections in a range beef cattle herd.

Bovine viral diarrhea virus (BVDV) infections resulting in clinical disease developed in calves, despite vaccination of dams and high maternal BVDV antibody titers in calves. Eight persistently infected (PI) calves born to immunocompetent dams were identified in the herd. Neutralizing BVDV antibody titers of PI calves had decreased greatly by the time the calves were 1 to 2 months old. Antibody titers of PI calves decreased more rapidly than antibody titers of calves that were not PI. Reduced antibody titers in PI calves allowed detection of BVDV in serum specimens of all PI calves by the time they were 8 weeks old. Persistent infection in suspect calves was detectable serologically and was confirmed by virologic examination of serum specimens 4 months after weaning, when the calves were 9 months old. Growth rates were reduced in viremic calves.

Animals

Tumour necrosis factor alpha in gingival crevicular fluid as a possible indicator of periodontal disease in humans.

The suitability of using the cytokine TNF as an indicator of periodontal disease was assessed. Gingival crevicular fluid was collected from 162 sites on filter strips and analysed for TNF by ELISA. About 21% of the sites contained TNF: the amount recovered per site ranged from 0.2 to 998.8 fmol with a median value of 3.7 fmol. The periodontal disease status of each site was documented by recording the gingival and plaque indices, and by measuring pocket depth. About 62% of TNF-containing sites had a gingival index of 1, 76% had a plaque index of 0 or 1, and 47% had pockets of 3 mm or less. When the periodontal status of sites with and without TNF was compared by chi 2 analysis, no significant differences were found. These findings suggest that TNF may be found in sites prior to clinically observable disease and therefore may prove to be a suitable indicator for periodontal disease.

Enzyme-Linked Immunosorbent Assay

Genetic comparison of ovine and bovine pestiviruses.

Viral RNA oligonucleotide fingerprinting was used to compare genetic relationship among pestiviruses originating from ovine or bovine host species. Ovine pestiviruses, including reference border disease virus and 2 border disease isolates originating from natural pestivirus infections of sheep, appeared to have a more distant genetic relationship among themselves than with certain bovine pestiviruses. A closer genetic relatedness was evident between border disease virus and 3 noncytopathic bovine pestiviruses, including Draper bovine viral diarrhea virus (BVDV), a BVDV isolate that originated from aborted bovine fetuses, and a virus that was isolated from the serum of a calf that had a chronic BVDV infection. Four noncytopathic bovine viruses, including Draper BVDV and 3 field isolates, were closely related. Reference Oregon C24V BVDV, a cytopathic virus, was closely related to only 1 of the 7 noncytopathic viruses in this study.

Animals

Faculty status in a climate of change.

Schools of dentistry that continue to conduct predoctoral dental education programs were surveyed to determine the status of full-time faculty and permit a comparison to responses made in 1980 to the identical survey. The response rate was 72.7 percent and included a representative distribution of schools. Since 1980, there has been a decrease in the number of full-time clinical faculty while at the same time the proportion of clinical faculty with tenure has increased. The development of dual tracks and the appointment of full-time, nontenure-trackfaculty forecasted in 1980 has come to fruition. Such appointments represent an increasing proportion of clinical faculty. The mean age of faculty has not changed appreciably due primarily to early retirement, and the five-year turnover rate remains relatively constant at 33 percent. Dental schools, at least as reflected in the tenure review process, would appear to be imposing more stringent expectations for scholarship. This finding, coupled with the growing concern that in the future there will be a shortage of adequately trained clinical faculty capable of entering the mainstream of biomedical or behavioral research within academic health centers poses a challenge for all concerned with the viability of dental faculties.

Faculty, Dental

Implantation and diabetes: analysis of 525 cases.

This is a retrospective study of 525 posterior chamber implants in diabetics performed by A S M Lim and B C Ang of Singapore. The patients were reviewed by visiting ophthalmologists--J E Kennedy (Sydney), M Ngui (East Malaysia) and P M Hart (Belfast). This study did not show any significant difference in the complication of post-operative visual acuity between diabetics and non-diabetics. 95% obtained 6/12 vision or better when pre-existing disease was excluded. It also showed that posterior chamber implants can be inserted in eyes with maculopathy or proliferative retinopathy if laser treatment was effectively done before or after surgery.

Adult