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D Kuhl

Publications and source records attributed to D Kuhl.

At least 19 recordsLinked to original sources
PubMed1996

A different form of long-lasting potentiation revealed in tissue plasminogen activator mutant mice.

The establishment of hippocampal long-term (LTP) requires protein and mRNA synthesis, suggesting that neuronal activity resulting in LTP initiates a cascade of gene expression. The expression of the gene for the extracellular serine protease tissue plasminogen activator (t-PA) is induced during LTP. Here we analyze long-lasting LTP (L-LTP,>4 hr)in CA1 hippocampal slices of mice homozygous for disrupted t-PA genes. Although mutant mice appear to exhibit long-term potentiation, we provide evidence that these mice are devoid of conventional homosynaptic L-LTP at the Schaffer collateral-CA1 pyramidal cell synapse. Most remarkably, t-PA-deficient mice exhibit a different form of long-lasting potentiation that is characterized by an NMDA receptor-dependent modification of GABA transmission in the CA1 region.

2-Amino-5-phosphonovalerate↗
PubMed1996

Prostatic acid phosphatase levels (enzymatic method) from completely sectioned, clinically benign, whole prostates.

Clinically benign, whole untrimmed prostates were obtained from 104 patients at autopsy, completely sectioned, and examined microscopically. The histological and gross findings of the prostate were correlated with premortem prostatic acid phosphatase levels (PAP, enzymatic method, ACA, Dupont Co.) to determine how often carcinoma of the prostate (CAP) affected PAP levels and to identify other findings within the prostate associated with elevated PAP levels. Sixty (58%) prostates did not have CAP, 34 (33%) had CAP smaller than 1 ml in volume, and 10 (10%) had CAP larger than 1 ml in volume. PAP levels were elevated (greater than 1 U/L) in 8 of 60 (13%) prostates without CAP, in 2 of the 34 (6%) prostates with CAP smaller than 1 ml, and in 1 of the 10 (10%) prostates with CAP larger than 1 ml. These differences were not statistically significant. Likewise, a statistically significant correlation between PAP levels and patient age, patient race, severe inflammation, of high grade prostatic intraepithelial neoplasia (PIN) was not found. However, there was a statistically significant correlation between PAP levels and prostate weight (p < 0.0001). This study suggest that PAP cannot distinguish between patients with clinically undetected CAP and patients without CAP. Furthermore, elevated PAP levels are often not due to metastatic CAP and additional evidence should be present, even in patients with known CAP, before an elevated PAP level is considered to be conclusive evidence of metastatic CAP.

Acid Phosphatase↗
PubMed1995

The vesicular monoamine transporter is not regulated by dopaminergic drug treatments.

The number of neuronal synaptic vesicular monoamine transporters (vesicular monoamine transporter type 2; VMAT2) has been recently proposed as an index of monoamine presynaptic terminal density. The present study investigated the possible regulation of the vesicular monoamine transporter. Rats were treated for 2 weeks with drugs known to influence dopaminergic neurotransmission, including those commonly used in the treatment of Parkinson's disease. Autoradiographic assays were performed using [3H]methoxytetrabenazine, [3H]raclopride, and [3H]WIN 35,428 ([3H]2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane) to measure vesicular monoamine transporter, dopamine D2 receptor and synaptic plasma membrane dopamine re-uptake site bindings, respectively. None of the drug treatments significantly modified levels of vesicular monoamine transporter binding. In contrast, both dopamine D2 receptors and dopamine re-uptake sites were altered by some of the treatment regimens. These data extend preliminary results that suggest the vesicular monoamine transporter is not easily regulated and confirm the plasticity of dopamine D2 receptors and the dopamine re-uptake site. Measures of striatal vesicular monoamine transporter density may, thus, provide objective estimates of monoaminergic innervation in neurodegenerative diseases, unaffected by the use of symptomatic therapies.

Animals↗
PubMed1995

Somatodendritic expression of an immediate early gene is regulated by synaptic activity.

Trans-synaptic activation of gene expression is linked to long-term plastic adaptations in the nervous system. To examine the molecular program induced by synaptic activity, we have employed molecular cloning techniques to identify an immediate early gene that is rapidly induced in the brain. We here report the entire nucleotide sequence of the cDNA, which encodes an open reading frame of 396 amino acids. Within the hippocampus, constitutive expression was low. Basal levels of expression in the cortex were high but can be markedly reduced by blockade of N-methyl-D-aspartate receptors. By contrast, synaptic activity induced by convulsive seizures increased mRNA levels in neurons of the cortex and hippocampus. High-frequency stimulation of the perforant path resulted in long-term potentiation and a spatially confined dramatic increase in the level of mRNA in the granule cells of the ipsilateral dentate gyrus. Transcripts were localized to the soma and to the dendrites of the granule cells. The dendritic localization of the transcripts offers the potential for local synthesis of the protein at activated postsynaptic sites and may underlie synapse-specific modifications during long-term plastic events.

Amino Acid Sequence↗
PubMed1995

Evaluation of age-specific normal ranges for prostate-specific antigen.

OBJECTIVES: To compare the traditional normal range (TNR) of 0.0 to 4.0 ng/mL for serum prostate-specific antigen (PSA) to age-specific normal ranges (ASNRs). METHODS: An autopsy series of completely sectioned, clinically benign prostates from 171 consecutive Caucasian men over the age of 40 years was selected. These patients were divided into those having no prostate cancer at autopsy, prostate cancer less than 1 cc in volume, and prostate cancer at least 1 cc in volume. The PSA values of each group were compared using both the TNR and the ASNR. RESULTS: Twenty-three of 105 (21.9%) patients with no cancer had elevated PSA values by the TNR, whereas only 18 (17.1%) were elevated using the ASNR. Nine of 54 (16.7%) with cancer less than 1 cc were elevated using the TNR, and 7 of 54 (13.0%) using the ASNR. Of 12 patients with cancer at least 1 cc, all had elevated PSA levels using the TNR and 11 (91.7%) were elevated using the ASNR. All discrepancies between the TNR and ASNR occurred in the 60- to 79-year age range. CONCLUSIONS: Use of ASNRs appears helpful in increasing the specificity of PSA by eliminating some elevated values in patients in their 60s and 70s.

Adult↗
PubMed1995

Patterns of care in advanced HIV disease in a tertiary treatment centre.

A retrospective chart review of all in-patient deaths in 1992 was undertaken to examine patterns of care in advanced HIV disease at St Paul's Hospital, Vancouver, Canada. St Paul's Hospital cares for approximately 75% of the Province of British Columbia's AIDS caseload. This represents about 18% of Canada's caseload. Data were collected on demographic characteristics, the utilization of home care and community services, income and social support, symptom presentation at terminal admission and the utilization of acute hospital care and hospital based palliative care. A total of 126 deaths were reviewed. All but two subjects were homosexual/bisexual men. The median age at death was 39 years (range 24-67). Four patterns of care at death were identified: (1) aggressive therapy with resuscitation 24 (19%), (resuscitation was initiated in 58%); (2) aggressive therapy with a no resuscitation order 49 (39%), in which the palliative period was a median of three days; (3) death on the palliative care unit 33 (29%), with a median survival once palliative of 20 days; and (4) death on the palliative care unit following respite admissions 16 (13%), with a median survival once palliative of 64 days. Despite a well known and respected Palliative Care Unit and community palliative care programme, there is a marked trend towards death occurring during aggressive therapy with a 200% increase in the initiation of resuscitation compared to the previous three years. No-one has been discharged alive from hospital following the initiation of resuscitation since 1988. This study illustrates the need for providers and persons infected with HIV to reconsider expectations about treatment outcomes in advanced HIV disease.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Cloning and characterization of two related serotonergic receptors from the brain and the reproductive system of Aplysia that activate phospholipase C.

Serotonin (5-HT) plays important roles in various behavioral and physiological processes in Aplysia californica. These include feeding, locomotion, circadian rhythm, learning and memory, synaptic plasticity, and synaptic growth. Serotonin modulates these various functions by interacting with different 5-HT receptor subtypes that are coupled to various second-messenger systems. We report here the isolation and characterization of the first two serotonergic receptors from Aplysia californica, Ap5-HTB1 and Ap5-HTB2, using a strategy based on the amino acid sequence homology among G-protein-coupled biogenic amine receptors. Ap5-HTB1 and Ap5-HTB2 are both intronless and highly homologous to each other, sharing 79.5% sequence identity at the amino acid level. Sequence comparison reveals that these receptors are 33.1 to 23.3% identical to the following 5-HT receptors: 5-HTdro1 > 5-HT6 > 5-HTlym > mouse 5-HT1B > 5-HTdro2A > mouse 5-HT7 > rat 5-HT2A. Both Ap5-HTB1 and Ap5-HTB2 encode functional 5-HT receptors. When expressed in cultured cells, these receptors stimulate phospholipase C in response to 5-HT in a dose-dependent manner. This stimulation can be blocked by specific 5-HT receptor antagonists. Using RT-PCR and Western blot analysis, we have detected these receptors in the CNS (Ap5-HTB2) and in the reproductive system (Ap5-HTB1). The nucleotide sequences of Ap5-HTB1 and Ap5-HTB2 were submitted to GenBank; the accession numbers are L43557 and L43558, respectively.

Amino Acid Sequence↗
PubMed1995

The incidence of unsuspected metastases from clinically benign prostate glands with latent prostate carcinoma.

OBJECTIVE: To determine how many latent prostate gland carcinomas (unsuspected carcinomas in clinically benign prostate glands) metastasize. DESIGN: The prostate glands and the pelvic and paraaortic lymph nodes were removed at autopsy from 209 consecutive patients with clinically benign prostate glands. The prostate glands were completely sectioned and examined microscopically using full cross sections. Pelvic and para-aortic lymph nodes were identified and examined microscopically for metastases. RESULTS: Seventy-nine (38%) of the prostate glands had latent prostate carcinomas. None of the pelvic or paraaortic lymph nodes contained metastases. CONCLUSION: This study suggests that few latent prostate-gland carcinomas metastasize.

Aged↗
PubMed1994

Incidence, racial differences, and prognostic significance of prostate carcinomas diagnosed with obstructive symptoms.

BACKGROUND: It is unknown how often prostate carcinomas are diagnosed as a result of urinary obstructive symptoms or whether prostate carcinomas diagnosed because of obstructive symptoms have a favorable or unfavorable prognosis. It is also unknown whether racial differences in obstructive symptoms could help explain why black men with prostate carcinoma are diagnosed with more advanced stages and grades of prostate carcinoma than are white men with prostate carcinoma. METHOD: At a single Veterans Administration Medical Center, 478 consecutive cases of prostate carcinoma diagnosed between 1973 and 1985 were identified. The incidence of obstructive symptoms at diagnosis, racial differences in obstructive symptoms, and the survival of patients with and without obstructive symptoms, stratified by stage and grade, were determined. In addition, racial differences in the frequency of surgical intervention required to relieve the obstructive symptoms were determined. RESULTS: All patients diagnosed with Stage A prostate carcinoma and most (82%) patients diagnosed with Stage C prostate carcinoma had obstructive symptoms. Those diagnosed with Stage B and Stage D prostate carcinomas had with similar frequencies (53% and 55%, respectively) of obstructive symptoms. Survival, stratified by stage and grade, was similar for men with and without obstructive symptoms. The incidences of obstructive symptoms and the frequency of surgical intervention to relieve the obstructive symptoms, stage for stage, were similar for white and black men. CONCLUSION: Survival, stratified by stage and grade, is not affected adversely by obstructive symptoms. Neither racial differences in the incidence of obstructive symptoms nor the frequency with which obstructive symptoms require surgical correction explain why black men with CAP consistently are diagnosed more frequently with Stage D prostate carcinoma and less frequently with Stage A CAP than white men with CAP.

Adult↗
PubMed1994

Characteristics of prostatic infarcts and their effect on serum prostate-specific antigen and prostatic acid phosphatase.

OBJECTIVES: To determine how prostatic infarcts affect serum prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels. METHODS: Two hundred eighteen clinically benign, whole prostates were obtained at autopsy, completely sectioned, and examined histologically. PSA and PAP levels were determined from premortem serum. RESULTS: Six of the 218 (2.8%) prostates had infarcts. The infarcts were usually multiple and usually located in the central and/or middle concentric zones of the middle third of the prostate without a preference for a particular lobe. Serum PSA by immunoradiometric assay were elevated in all 6 cases. Serum PAP by both enzymatic assay (ACA), and immunoradiometric assay were available for 5 cases and were elevated by both methods in 2 cases, approached elevated levels by both methods in 1 case, and were normal by both methods in 2 cases. The PSA and PAP levels appeared to be affected more by the age than by the size of the infarct. CONCLUSIONS: Prostatic infarcts elevate PSA levels more frequently than PAP levels, and prostatic infarcts may be responsible for some unexplained elevations of serum PSA and PAP levels.

Acid Phosphatase↗
PubMed1994

The visitor.

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Christianity↗
PubMed1993

Tissue-plasminogen activator is induced as an immediate-early gene during seizure, kindling and long-term potentiation.

The requirement of protein and messenger RNA synthesis for long-term memory suggests that neural activity induced by learning initiates a cascade of gene expression. Here we use differential screening to identify five immediate-early genes induced by neuronal activity. One of these is tissue-plasminogen activator (tPA), an extracellular serine protease, which is induced with different spatial patterns in the brain by three activity-dependent events: (1) convulsive seizure increases expression of tPA in the whole brain; (2) stimulation of the perforant path produces an epileptiform after-discharge that ultimately leads to kindling increases the levels of tPA throughout the hippocampus bilaterally; and (3) brief high-frequency stimulation of the perforant path that produces long-term potentiation (LTP) causes an NMDA (N-methyl-D-aspartate) receptor-mediated increase in the levels of tPA mRNA which is restricted to the granule cells of the ipsilateral dentate gyrus. As release of tPA is correlated with morphological differentiation, the increased expression of tPA may play a role in the structural changes that accompany activity-dependent plasticity.

3T3 Cells↗
PubMed1992

Long-term sensitization training in Aplysia leads to an increase in calreticulin, a major presynaptic calcium-binding protein.

Long-term memory for sensitization in Aplysia requires new protein and RNA synthesis. Here, we identify a late protein as calreticulin, the major Ca(2+)-binding protein of the lumen of the endoplasmic reticulum. An antiserum against Aplysia calreticulin reveals an enrichment of calreticulin immunoreactivity in presynaptic varicosities. Quantitative S1 nuclease analysis indicates that the steady-state level of calreticulin mRNA in Aplysia sensory neurons increases during the maintenance phase of long-term sensitization. The finding that this mRNA increases in expression late, some time after training, is consistent with the idea that long-term neuromodulatory changes underlying sensitization may depend on a cascade of gene expression in which the induction of early regulatory genes leads to the expression of late effector genes.

Amino Acid Sequence↗
PubMed1992

Long-term sensitization training in Aplysia leads to an increase in the expression of BiP, the major protein chaperon of the ER.

Long-term memory for sensitization of the gill- and siphon-withdrawal reflexes in Aplysia californica requires RNA and protein synthesis. These long-term behavioral changes are accompanied by long-term facilitation of the synaptic connections between the gill and siphon sensory and motor neurons, which are similarly dependent on transcription and translation. In addition to showing an increase in over-all protein synthesis, long-term facilitation is associated with changes in the expression of specific early, intermediate, and late proteins, and with the growth of new synaptic connections between the sensory and motor neurons of the reflex. We previously focused on early proteins and have identified four proteins as members of the immunoglobulin family of cell adhesion molecules related to NCAM and fasciclin II. We have now cloned the cDNA corresponding to one of the late proteins, and identified it as the Aplysia homolog of BiP, an ER resident protein involved in the folding and assembly of secretory and membrane proteins. Behavioral training increases the steady-state level of BiP mRNA in the sensory neurons. The increase in the synthesis of BiP protein is first detected 3 h after the onset of facilitation, when the increase in overall protein synthesis reaches its peak and the formation of new synaptic terminals becomes apparent. These findings suggest that the chaperon function of BiP might serve to fold proteins and assemble protein complexes necessary for the structural changes characteristic of long-term memory.

Amino Acid Sequence↗
PubMed1991

Prostate-specific antigen levels from completely sectioned, clinically benign, whole prostates.

Clinically benign whole, untrimmed prostates and pelvic lymph nodes were obtained from 105 patients at autopsy. All 105 patients had premortem serum from which prostate-specific antigen (PSA) levels were obtained. Sixty-eight did not have carcinoma of the prostate (CAP), 28 had CAP less than 1 ml and 9 had CAP larger than 1 ml. Eleven untrimmed prostates weighed 80 g or more and eight had elevated PSA levels (more than 4.0 ng/ml): five of eight without CAP, two of two with CAP less than 1 ml, and one of one with CAP larger than 1 ml. Ninety-four whole untrimmed prostates weighed less than 80 g and 20 had elevated PSA levels: ten of 60 without CAP, two of 26 with CAP less than 1 ml, and eight of eight with CAP larger than 1 ml. This study suggests that PSA levels from patients with untrimmed prostates weighing 80 g or more (equivalent to a 60-g trimmed prostate) are usually elevated regardless whether CAP is present. However, CAP less than 1 ml, in untrimmed prostates less than 80 g, usually does not elevate PSA levels whereas CAP larger than 1 ml usually does (P less than 0.0001). The likelihood that elevated PSA levels, from patients with untrimmed prostates less than 80 g, are due to CAP larger than 1 ml increases as the PSA level increases.

Adult↗
PubMed1990

Different pathways mediate virus inducibility of the human IFN-alpha 1 and IFN-beta genes.

Multimerization of GAAANN generates sequences frequent in virus-inducible promoters. We distinguished different types of (GAAANN)4 sequences mediating virus inducibility. Type I (NN = GT, GC, CT, or CC) responds to IFNs and to IRF-1 and causes silencing. Type II (NN = TG) and type III (NN = CG) neither silence nor respond to IRF-1 or IFN. Type III mediates constitutive transcription and binds the constitutive IEFga factor, whereas type II binds the novel "TG protein". IFN-beta and IFN-alpha 1 promoters contain different response elements: The former has a type I-like sequence (PRDI) and an NF-kappa B-binding sequence (PRDII); the latter has a type II-like "TG sequence" and possibly additional elements but does not bind NF-kappa B. Type I, type II, and NF-kappa B elements represent three distinct terminal pathways mediating virus induction.

Animals↗
PubMed1990

Stage D1 prostate carcinoma. The histologic appearance of nodal metastases and its relationship to survival.

Eighty-two of 307 consecutive staging lymphadenectomies had nodal metastases (Stage D1 prostate carcinoma). Seventy-seven of the 82 cases had at least a 5-year follow-up and 50 had at least a 10-year follow-up. Three of these 77 cases had Grade 1 (well-differentiated) metastases, 59 (77%) had Grade 2-3 (moderately differentiated) metastases, and 15 (19%) had Grade 4 (poorly differentiated) metastases (M. D. Anderson Hospital [MDAH] grading system). The patients with moderately differentiated metastases had 5-year and 10-year survival rates of 79% and 34%, respectively, whereas the patients with poorly differentiated metastases had 5-year and 10-year survival rates of 13% and 0%, respectively (P less than 0.0001). This study demonstrates a statistically significant difference between the prognosis of Stage D1 patients with moderately differentiated metastases and Stage D1 patients with poorly differentiated metastases. Consequently, the evaluation of the histologic appearance of Stage D1 metastases may be of clinical importance.

Carcinoma↗