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Biomedical subjects

K L Hall

Publications and source records attributed to K L Hall.

At least 19 recordsLinked to original sources
PubMed2005

Rat synapsin 1 promoter mediated transgene expression in testicular cell types.

Previous reports described the rat synapsin 1 promoter as primarily neuron selective. However, ectopic expression of a transgene under the rat synapsin 1 promoter was also detected in testis from some transgenic mouse lines. Here we investigate which cells within the testis express a transgene consisting of the rat synapsin 1 promoter fused with luciferase. Synapsin 1-luciferase expression vectors were introduced into HeLa cells, into TM3 cells derived from mouse testicular Leydig cells, and into one-cell embryos to make transgenic mice. Indirect immunofluorescence suggests that nontransfected TM3 cells do not express endogenous synapsin 1. TM3 stable transfectants, however, expressed luciferase under the direction of the synapsin 1 promoter, in both promoter orientations. HeLa cells displayed only low levels of activity. Transgenic mice carrying the synapsin 1-luciferase construct displayed high levels of luciferase activity in the brain, spinal cord, and testis. Enriched populations of prepuberal types A and B spermatogonia and adult Leydig cells, pachytene spermatocytes, and round spermatids prepared from transgenic mice all displayed substantial luciferase activity. Thus, the rat synapsin 1 promoter can mediate reporter gene expression in neurons and testicular cell types.

Animals↗
PubMed2001

Neuroleptic malignant syndrome due to olanzapine.

Neuroleptic malignant syndrome (NMS) is a rare and potentially fatal complication precipitated by the use of antipsychotic medications, most notably haloperidol. Criteria previously described include: exposure to the neuroleptic class of medications; hyperthermia; muscle rigidity; a cluster of laboratory and physical findings that may include mental status changes, autonomic instability, creatine phosphokinase elevation and leukocytosis, and exclusion of other causes for the patient's condition. A prodrome of mental status changes, autonomic instability, tremors, diaphoresis, excess salivation, and extrapyramidal signs may precede NMS. Prior reports of NMS linked to olanzapine have been in patients who had been previously treated with other neuroleptic agents or in patients who had previous episodes of NMS precipitated by other neuroleptics. Several cases included patients treated with olanzapine in addition to another neuroleptic. This report describes a case of NMS associated with olanzapine in a patient who had not previously been exposed to the neuroleptic drug class. At the time this patient presented, there were no reports in the literature of NMS associated with olanzapine alone. Treatment of NMS includes: immediate withdrawal of all neuroleptics; supportive care; fever control; management of autonomic instability (tachycardia, tachypnea, blood pressure fluctuations); and pharmacologic management with dantrolene and bromocriptine.

Adult↗
PubMed1999

Primary peritoneal psammocarcinoma: A case presenting with an upper abdominal mass and elevated CA-125.

Primary peritoneal serous adenocarcinoma with predominating psammoma bodies, psammocarcinoma, is a very rare tumor with only seven cases documented in the English literature. Pathological classification of this entity was established in 1990 and clinical behavior of this tumor is uncertain. Based on limited data these tumors appear to behave similarly to low malignant potential tumors of the ovary. This case describes a 59-year-old woman who underwent exploratory laparotomy for a large upper abdominal cystic mass. Findings included a large tumor mass involving the gastrocolic omentum and dense small bowel adhesions. The patient had normal ovaries and was debulked to no macroscopic disease. Final pathologic diagnosis confirmed a stage IIIC primary peritoneal psammocarcinoma. The patient has received no adjunctive therapy and is without evidence of disease 2 years after surgery. Primary peritoneal psammocarcinoma is a neoplasm which can mimic serous adenocarcinoma of the ovary. In contrast, primary peritoneal psammocarcinoma appears to behave in an indolent fashion. Primary surgical debulking should be attempted, while the utility of postoperative chemotherapy remains unknown.

Abdomen↗
PubMed1997

Analysis of Ki-ras, p53, and MDM2 genes in uterine leiomyomas and leiomyosarcomas.

Uterine sarcomas are unusual neoplasms of the female genital tract whose molecular etiology is largely unknown. We examined 20 leiomyomas as well as 23 uterine leiomyosarcomas for the presence of mutations in the Ki-ras and p53 genes, and overexpression of the MDM2 gene. Codons 12, 13, and 61 from the Ki-ras gene were characterized for the presence of mutations by restriction enzyme polymorphisms using mismatched primers and nucleic acid sequencing as appropriate. Activated Ki-ras genes were identified in 3/20 leiomyomas and 0/23 leiomyosarcomas. The p53 gene was analyzed by SSCP, nucleic acid sequencing, and immunohistochemical staining. None of 20 leiomyomas and 6/23 leiomyosarcomas exhibited p53 abnormalities. The SSCP/sequencing results did not consistently correlate with the IHC staining. MDM2 overexpression occurred in 0/20 leiomyomas and 3/23 sarcomas. Clinical correlation suggested that tumors with p53 mutations have a higher histologic grade or stage at presentation. We conclude that leiomyomas and leiomyosarcomas have different patterns of molecular alterations and are separate biologic entities. In addition, p53 and MDM2 overexpression may play a role in the development of a subset of leiomyosarcomas.

DNA, Neoplasm↗
PubMed1997

Villoglandular adenocarcinoma of the cervix: a report of three cases and review of the literature.

Villoglandular adenocarcinoma of the cervix is a distinct histologic type of cervical cancer. Fewer than 60 cases have been reported in the literature. Previous reports suggest that, due to the highly favorable prognosis of this rare histologic type of cervical cancer, conservative surgical therapy with cervical conization or extrafascial hysterectomy alone may be undertaken. In this series, three cases of villoglandular adenocarcinoma of the cervix are described. Preoperatively in each case, the cancer was confined to the cervix and histologic well-differentiated villoglandular adenocarcinoma of the cervix was confirmed. Extended hysterectomy was performed in all cases. In one case, residual invasive endocervical adenocarcinoma was noted. Careful review of the histologic characteristics of these tumors is needed when deciding if these patients can be managed with conservative therapy.

Adenocarcinoma↗
PubMed1997

Influenza control in acute care hospitals.

BACKGROUND: Influenza causes increased morbidity and mortality among patients in longterm care facilities, but little information is available on the impact of influenza in acute care settings. We wished to have such information when revising our hospital influenza control policy. METHODS: We reviewed recent reports of influenza among patients in acute care hospitals and surveyed large (approximately 500-bed) acute care teaching hospitals by telephone to determine the nature of their influenza control policies. RESULTS: Seventeen reports of influenza outbreaks in acute care hospitals were published from 1959 to 1994. Influenza A caused 13 of these outbreaks. Five involved children and 12 involved adults. The mean number of patients in each outbreak was 14 (range 1 to 49), with a mortality rate of 0% to 50% (median 0%, mean 6.5%). Health care workers were implicated in transmission in five reports. Vaccine was used infrequently during the outbreaks, and use of chemoprophylaxis was not reported. Our survey of current practices in 15 university-affiliated hospitals from 12 states revealed that all offered vaccine in the fall but none required either immunoprophylaxis or chemoprophylaxis at any time. Only three had formal policies detailing management of influenza in the hospital. CONCLUSIONS: Nosocomial influenza in acute care hospitals is infrequently reported and associated with a low mortality rate. Health care workers rarely comply with preventive measures, and few institutions have formal influenza control policies.

Acute Disease↗
PubMed1996

Distinct rat aortic smooth muscle cells differ in versican/PG-M expression.

Smooth muscle cells (SMCs) with distinct phenotypes are present in blood vessels, and distinct culture types appear when SMCs are maintained in vitro. For example, cultured SMCs from rat adult media grow as bipolar cells, which differ in gene expression from the predominantly cobblestone-shaped SMCs from rat pup aortas and rat neointimas that we call pi SMCs. Since proteoglycans are present at different concentrations in the normal intima and media and are elevated in atherosclerotic plaque, we sought to determine whether pi and adult medial SMC types synthesize different or unique proteoglycans that are characteristic of each phenotype. [35S]sulfate-labeled proteoglycans were purified by ion-exchange chromatography. An adult medial SMC line synthesized a large proteoglycan (0.2 Kav on Sepharose CL-2B) that was not detectable in a pi SMC line. Digestion of this proteoglycan with chondroitin ABC lyase revealed three core glycoproteins of 330, 370, and 450 kD. By Western blot analysis, the two smallest of these reacted with two antibodies to the human fibroblast proteoglycan versican. RNAs hybridizing to versican probes were found only in adult medial-type SMCs, including an adult medial type clone from pup aorta, by Northern blot analysis. Both SMC types synthesize RNAs that hybridize to probes for other proteoglycans, such as perlecan, biglycan, and decorin. We conclude that rat pi SMC cultures, unlike monkey, human, and rat adult medial SMC cultures, express little or no versican. This difference in expression may be responsible for the different morphologies and growth properties of the two cell types.

Age Factors↗
PubMed1995

Characterization of a functional angiotensin IV receptor on coronary microvascular endothelial cells.

A new class of angiotensin receptors has recently been identified that exhibits both high specificity and affinity for the hexapeptide (3-8) fragment of angiotensin II, angiotensin IV (AngIV). Here, utilizing radioligand binding, we fully characterize AngIV binding at the AT4 receptor on cultured bovine coronary venular endothelial cells (CVEC), and report that when AngIV and bFGF are presented simultaneously an enhancement of DNA synthesis results that is significantly greater than that produced by bFGF alone. The level of DNA synthesis was determined by the incorporation of [3H]thymidine into quiescent CVEC monolayers following exposure to 10 nM AngIV and 10 ng/ml bFGF for 1, 3, 5, 7, 9, or 11 days. A significant enhancement of DNA synthesis (P < 0.01) was seen following 3, 5, 7, 9 and 11 days exposure. In addition, AngIV does not bind to bFGF or heparin, and conversely, bFGF is unable to compete for AngIV binding which suggests that this synergistic response is mediated by independent receptors for these ligands. Results of this study indicate that microvascular endothelial cells are significantly more responsive to bFGF in the presence of nanomolar concentrations of AngIV.

Amino Acid Sequence↗
PubMed1994

The effects of masking on the growth of vibrotactile sensation magnitude and on the amplitude difference limen: a test of the equal sensation magnitude-equal difference limen hypothesis.

In this study, the hypothesis that the difference limen (DL) for the detection of differences in amplitude of vibrotactile stimuli is independent of the slope of the sensation magnitude function was tested. The slope of the sensation magnitude function was varied by presenting test stimuli in the presence of or in the absence of vibrotactile noise. The slopes of the sensation magnitude functions were determined through a matching technique in which the subject adjusted stimulus amplitudes of a 250-Hz stimulus presented alone and a 250-Hz stimulus presented simultaneously with a masking noise, so that their sensation magnitudes were equated. The slope of the matching function was found to increase as a function of the intensity of the masking noise. In the second phase of the experiment, the amplitude DL was measured by the gated-pedestal method for test stimuli presented under the same stimulus conditions as used in the matching procedure. At all levels of stimulus intensity, the DL was found to be independent of the masking condition provided the sensation magnitudes of the stimuli were the same. This finding supports the hypothesis that the size of the DL is independent of the slope of the sensation magnitude function, provided the sensation magnitudes of stimuli are the same. The generality of this principle, first discovered in hearing, is thus extended to another sense modality.

Auditory Perception↗
PubMed1994

The effects of aging on information-processing channels in the sense of touch: I. Absolute sensitivity.

Thresholds for detecting vibrotactile signals of variable frequency applied to the thenar eminence of the hand by small and large contactors were measured in subjects ranging in age from 10 to 89 years. Thresholds were found to increase as a function of age, but the rate of increase was greater after than before the age of 65 years. The rate of loss of vibrotactile sensitivity was substantially greater in the P channel (mediated by Pacinian corpuscles) than in the NP I channel (mediated by rapidly adapting fibers), the NP II channel (mediated by slowly adapting type II fibers), or the NP III channel (mediated by slowly adapting type I fibers). Women were frequently found to have greater sensitivity than men.

Adolescent↗
PubMed1993

Identification and characterization of a novel angiotensin binding site in cultured vascular smooth muscle cells that is specific for the hexapeptide (3-8) fragment of angiotensin II, angiotensin IV.

This study demonstrates the existence of a previously unrecognized class of angiotensin binding sites on vascular smooth muscle that exhibit high affinity and specificity for the hexapeptide (3-8) fragment of angiotensin II (AngIV). Binding of [125I]AngIV is saturable, reversible and describes a pharmacologic profile that is distinct and separate from the classic AT1 or AT2 angiotensin receptors. Saturation binding studies utilizing cultured vascular smooth muscle cells obtained from bovine aorta (BVSM) revealed that [125I]AngIV bound to a single high affinity site with an associated Hill coefficient of 0.99 +/- 0.003, exhibiting a KD = 1.85 +/- 0.45 nM and a corresponding Bmax = 960 +/- 100 fmol mg-1 protein. Competition binding curves in BVSM demonstrated the following rank order effectiveness: AngIV > AngII(3-7) >> AngIII > Sar1,Ile8 AngII > AngII > AngII(1-7) > AngII(4-8), DuP 753, PD123177. The presence of the non-hydrolyzable GTP analog GTP gamma S, had no effect on [125I]AngIV binding affinity in BVSM. The presence of this novel angiotensin binding site on smooth muscle in high concentration suggests the possibility that this system may play an important, yet unrecognized role in vascular control.

Amino Acid Sequence↗
PubMed1993

Elucidation of a specific binding site for angiotensin II(3-8), angiotensin IV, in mammalian heart membranes.

Data are presented describing a new angiotensin binding site in rabbit and guinea pig heart, distinct from AT1 and AT2, that demonstrates high specificity and affinity for the hexapeptide fragment angiotensin II(3-8), which will be referred to here as angiotensin IV (AIV). Equilibrium binding in rabbit heart membranes was achieved in 2 hr at 37 degrees C and produced a calculated kinetic KD of .174 +/- .018 nM. Saturation equilibrium binding data for rabbit and guinea pig heart were best fit to a one-site model with Hill coefficients near unity. Guinea pig membranes exhibited a KD = 1.33 +/- .02 nM and a Bmax = 144 +/- 19 fmol/mg protein, and rabbit heart membranes had a KD = 1.70 +/- .50 nM and a Bmax = 731 +/- 163 fmol/mg protein. The binding site showed a high specificity for AIV, although it exhibited low affinity for angiotensin II, angiotensin III, Sar1,Ile8-angiotensin II, DuP 753, CGP42112A and PD123177. A large number of nonangiotensin-related peptides were unable to compete effectively for 125I-AIV binding. Deletions made from the C-terminal end of AIV caused a decrease in affinity: AIV > AII(3-7) >> AII(3-6) >> AII(3-5). Extension of the C-terminal end of AIV corresponding to the amino acids of human angiotensinogen caused little change in affinity. GTP gamma S had no effect on binding, suggesting non-G protein linkage. Binding was widely distributed throughout the heart; it was observed on cardiocytes and blood vessels as well as in the epicardium and the endocardium.

Amino Acid Sequence↗
PubMed1993

Central angiotensin IV binding sites: distribution and specificity in guinea pig brain.

Our laboratory has reported previously that a unique binding site specific for the hexapeptide angiotensin (A)II(3-8), now referred to as AIV, is present in a number of tissues including bovine adrenal gland, rabbit and guinea pig heart and guinea pig kidney, liver, lung, uterus and brain. The present results extend previous findings in the guinea pig brain and identify binding sites for AIV in the neocortex, paleocortex, hippocampus, medial habenula, superior and inferior colliculi, caudate putamen, thalamus, dorsal tegmentum, central gray, red nucleus, inferior olivary, oculomotor and hypoglossal nuclei and cerebellum. Binding of [125I]AIV in selected regions was shown to be of high affinity (Kd = 0.60-1.47 nM), saturable (maximal number of binding sites = 181-449 fmol/mg of protein) and specific. This binding site was shown to be distinct from the AT1 and AT2 sites with Ki values > 10(-4) M for DuP 753, CGP42112A and PD123177. Changes at the N-terminal of the peptide, either by removal of the valine or by extension of the peptide, resulted in a large decrease in binding affinity. In contrast, C-terminal extensions resulted in little change in affinity for the binding site. Guanosine 5'-0-(3-thiotriphosphate) was shown to have no effect on binding, suggesting that the guinea pig brain binding site is not G-protein-linked. Potential functions associated with this newly discovered A binding site are discussed.

Amino Acid Sequence↗
PubMed1992

Discovery of a distinct binding site for angiotensin II (3-8), a putative angiotensin IV receptor.

We report here the discovery of a unique and novel angiotensin binding site and peptide system based upon the C-terminal 3-8 hexapeptide fragment of angiotensin II (NH3(+)-Val-Tyr-Ile-His-Pro-Phe-COO-) (AII(3-8) (AIV)). This fragment binds saturably, reversibly, specifically, and with high affinity to membrane-binding sites in a variety of tissues and from many species. The binding site is pharmacologically distinct from the classic angiotensin receptors (AT1 or AT2) displaying low affinity for the known agonists (AII and AIII) and antagonist (Sar1,Ile8-AII). Although a definitive function has not been assigned to this system in many of the tissues in which it resides, AIV's interaction with endothelial cells may involve a role in endothelial cell-dependent vasodilation. Consequent to this action, AIV is a potent stimulator of renal cortical blood flow.

Adrenal Cortex↗
PubMed1992

Identification of an AII(3-8) [AIV] binding site in guinea pig hippocampus.

A unique angiotensin binding site specific for the hexapeptide, AII(3-8), has been identified in guinea pig hippocampus. This binding site, which is present in the pyramidal cell layer of CA1, CA2, CA3 of the hippocampus and dentate gyrus, binds AII(3-8) with high affinity (KD = 1.29 +/- 0.18 nM) in a saturable manner (Bmax = 449 +/- 62 fmol/mg protein). The N-terminal structure of the binding ligand is paramount in determining the binding affinity. The C-terminal requirements seem less stringent as evidenced by the binding affinity of AII(3-7) (KD = 20.9 +/- 2.1 nM). Neither AII, AIII,Sar1, Ile8-AII, Dup 753 nor CGP42112A appear to bind, indicating that this binding site is neither the AT1 nor AT2 sites described for AII/AIII. Autoradiographic analysis of hippocampus binding confirms the inability of Sar1,Ile8-AII to compete for [125I]AII(3-8) binding. Conversely AII(3-8) was unable to displace [125I]Sar1,Ile8-AII binding.

Angiotensin II↗
PubMed1992

Panic disorder. Recognizing and managing the 'real thing'.

Panic disorder is a severe anxiety disease frequently encountered in primary care. Although it is associated with potentially serious medical and psychiatric complications and is often difficult to diagnose, the condition is highly treatable. Initial pharmacotherapy may include alprazolam (Xanax), imipramine hydrochloride (Janimine, Tofranil), or phenelzine (Nardil). Correct diagnosis and treatment can alleviate much suffering and expense and promote both mental and physical health.

Diagnosis, Differential↗