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PubMed1995

Patterns of localization and cytoskeletal association of two vegetally localized RNAs, Vg1 and Xcat-2.

In Xenopus, localization of a rare class of mRNAs during oogenesis is believed to initiate pattern formation in the early embryo. We have determined the pattern of RNA localization for one of these RNAs, Xcat-2, which encodes a putative RNA-binding protein related to Drosophila nanos (Mosquera, L., Forristall, C., Zhou, Y. and King, M. L. (1993) Development 117, 377-386). Xcat-2 is exclusively localized to the mitochondrial cloud in stage I oocytes, moves with this body into the vegetal cortex during stage II and, later, partitions into islands consistent with it being a component of the germ plasm. As previously shown, Vg1 is not localized to the vegetal cortex until stage IV and distributes to all vegetal blastomeres during development. We found a direct correlation between the localized condition of these RNAs and their recovery in a detergent-insoluble fraction. We present evidence suggesting that differential RNA binding to a cytoskeletal component(s) in the vegetal cortex determines the pattern of inheritance for that RNA in the embryo.

Animals↗
PubMed1981

Effects of variations in local reinforcement rate on local response rate in variable interval schedules.

Rats trained to lever press for sucrose were exposed to variable-interval schedules in which (i) the probability of reinforcement in each unit of time was a constant, (ii) the probability was high in the first ten seconds after reinforcement and low thereafter, (iii) the probability was low for ten seconds and high thereafter, (iv) the probability increased with time since reinforcement, or (v) the probability was initially zero and then increased with time since reinforcement. All schedules generated similar overall reinforcement rates. A peak in local response rate occurred several seconds after reinforcement under those schedules where reinforcement rate at this time was moderate or high ([i], [ii], and [iv]). Later in the inter-reinforcement interval, local response rate was roughly constant under those schedules with a constant local reinforcement rate ([i], [ii], and [iii]), but increased steadily when local reinforcement rate increased with time since reinforcement ([iv] and [v]). Postreinforcement pauses occurred on all schedules, but were much longer when local reinforcement rate was very low in the ten seconds after reinforcement ([iii]). The interresponse time distribution was highly correlated with the distribution of reinforced interresponse times, and the distribution of postreinforcement pauses was highly correlated with the distribution of reinforced postreinforcement pauses on some schedules. However, there was no direct evidence that these correlations resulted from selective reinforcement of classes of interresponse times and pauses.

Journal Article↗
PubMed1986

"Bi-digital o-ring test molecular identification and localization method" and its application in imaging of internal organs and malignant tumors as well as identification and localization of neurotransmitters and micro-organisms--Part 1.

Using the "Bi-Digital O-Ring Test Molecular Identification and Localization Method," one can identify and localize minute amounts of bioactive substances (including neurotransmitters), micro-organisms, toxic substances, or drugs, and, in addition, one can non-invasively image normal organs as well as screen for and image the distribution of specific types of cancer of specific internal organs without using any expensive instrumentation. One can also use this method to perform a qualitative analysis of neurotransmitters, neuromodulators, and hormones on different parts of the imaged organs. The molecule or substance being investigated is compared with a minute amount of a pure control reference substance, and if the substance identical to the control reference substance exists, then the electro-magnetic waves emitted by the identical substance will produce an electro-magnetic resonance phenomenon with the electro-magnetic waves of identical resonance frequency emitted by the control reference substance, and this resonance phenomenon is hypothesized to be the basis of the "Bi-Digital O-Ring Test Molecular Identification and Localization Method." The following substances have been used as control reference substances to identify and localize identical substances in vitro and in vivo: pure neurotransmitters (e.g. serotonin, beta-endorphin, methionine-enkephalin, norepinephrine, dopamine, L-dopa, substance P, etc.), as well as L-tryptophan and L-tyrosine; cholesterol; steroid hormones (including aldosterone, corticosterone, cortisol, progesterone, testosterone, etc.); peptide hormones; microscopic slides of normal organs; microscopic slides of specific cancer cells of specific organs (e.g. adenocarcinoma of the head of the pancreas, adenocarcinoma of the descending colon, etc.); microscopic slides of pure micro-organisms; toxic substances (e.g. lead, mercury, KCN); drugs (including non-steroidal anti-inflammatory drugs, antibiotics, beta-blockers, calcium channel blockers, etc.); and antibodies against specific substances or micro-organisms. An intensive network of serotonin and L-tryptophan was discovered, by using the "Bi-Digital O-Ring Test Molecular Identification and Localization Method," in different parts of the body. In general, in painful areas, frequently serotonin is markedly reduced, L-tryptophan is markedly increased, and substance P is markedly increased, while in non-painful areas, serotonin is markedly increased, L-tryptophan is markedly decreased, and substance P is markedly decreased.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

[Big-toe localizing test--clinical study of proprioceptive localization].

Certain proprioceptive sense is utilized in localizing a part of the limb passively held in space. In the previous study (Hirayama, Fukutake, et al., 1986), we demonstrated that such kind of proprioception, which we called "proprioceptive localization", could be detected by making the patient pick up the thumb with the opposite fingers (the thumb localizing test, TLT). As a further development of the TLT, another test, named a big-toe localizing test (BTLT), was devised. In the BTLT, the patient, with eyes closed and a lower limb passively immobilized by the examiner (the fixed limb), is asked to point to the big toe with the index finger of one hand or the other (the reaching limb). Firstly, we assessed the unselected series of 33 patients with thoracic or lumbar myelopathy regarding their sensory impairment and obtained the following conclusions on the BTLT similar to those in our previous study on the TLT. (1) BTLT deficits results from perceptive impairment in the fixed limb. (2) The perceptual information involved in the proprioceptive localization is different from that of the test for the appreciation of passive movement and posture. (3) On the basis of the correlation to other symptomatology, it is suggested that BTLT deficits arise from lesions of the posterior column-medical lemniscal system. (4) The BTLT is more sensitive than the test for the appreciation of passive movement and posture. Secondly, we evaluated another unselected series of 63 patients with unilateral TLT deficits due to CNS lesions. Eight patterns of BTLT deficits were identified and classified into 3 following types.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2003

[Future prospects for primary hormone therapy in localized and locally advanced prostate cancer].

The authors consider current and future prospects for primary hormone therapy in localized and locally advanced prostate cancer by comparing this form of treatment (hormone monotherapy) with neoadjuvant radiation therapy and radical prostatectomy. Neoadjuvant hormone therapy prior to radiation therapy has been proven effective in recent years, and currently the United States is showing a year-by-year increase in the use of androgen blocking agents during the early stage of prostate cancer. A survey of recent research findings, clearly showed that, for patients with localized prostate cancer, there is no significant difference in survival rate between hormone monotherapy and radical prostatectomy. In the future we can expect to see an increase in available treatment options for localized and locally advanced prostate cancer, with the optimal therapy for each individual patient to be selected by the attending physician in discussion with the patient.

Androgen Antagonists↗
PubMed2004

[Endocrine therapy for localized or locally advanced prostate cancer].

The place of endocrine therapy, either alone or in combination with radiotherapy and surgery, remains highly controversial in the treatment of non-metastatic prostate cancer. The authors review the results of isolated endocrine therapy or associated with local therapy. At the present time, there are few arguments in favour of the use of endocrine therapy in the following situations: isolated treatment of localized or locally advanced cancer prior to radical prostatectomy, after radical prostatectomy. Current data suggest a benefit of endocrine therapy in combination with radiotherapy in patients with high-grade localized or locally advanced cancer.

Androgen Antagonists↗
PubMed1978

Stimulation of resistance against local tumor growth, of hosts pretreated by combined local hyperthermia and X-irradiation.

The relationships involved in host resistance to tumor development were studied. Animals were pretreated by local hyperthermia, local irradiation and combined local hyperthermia and x-irradiation. After treatment, the animals were inoculated with tumor cells 0--96 or 0--120 hours post treatment. (BALB/c X C57B1/6)F1 mice were inoculated with the SV40 local fibrosarcoma, and (C3H/eB/B1)F1 mice were inoculated with the metastatic Lewis lung carcinoma. The results show an enhanced resistance to tumor development in animals pretreated by the combined simultaneous local heat and x-irradiation, as compared to animals only preirradiated, only preheated, or to control untreated tumor-bearing animals.

Animals↗
PubMed1989

[Local immunotherapy of breast cancer: a case of advanced breast cancer improved by combined local injection therapy with OK-432 and rIL-2].

An effective immunotherapy for breast cancer has yet to be established. We have recently experienced an inoperable case of advanced breast cancer due to mental disorder. Combined local injection therapy with OK-432 and rIL-2 was performed in addition to non-surgical multi-disciplinary treatment, with obvious therapeutic effects. The case is a 67-year-old female, who had a 5.0 x 4.7 cm tumor in the area A of the left mammary gland. Aspiration cytologic examination revealed class V breast cancer. Besides systemic chemotherapy, local injection therapy with OK-432 2.0 KE on day 1 and rIL-2 500 U on day 3 was performed. Upon starting local injection therapy, a rapid reduction was noted in the tumor diameter (reduction rate, 75.5%). Tumor makers of CEA, CA 15-3 also showed obvious diminution. Although the dose and interval of administration remain to be further examined, the combined local injection therapy with OK-432 and rIL-2 was suggested to be an effective local immunotherapy for breast cancer.

Adenocarcinoma, Scirrhous↗
PubMed1981

Amyloid in localized cutaneous amyloidosis: immunofluorescence studies with anti-keratin antiserum especially concerning the difference between systemic and localized cutaneous amyloidosis.

Amyloid of localized cutaneous amyloidosis and systemic amyloidosis were subjected to study with an indirect immunofluorescence technique using anti-keratin antiserum. Anti-keratin antiserum was prepared ad modum Sun & Green. Amyloid of localized cutaneous amyloidosis was positively stained for the antiserum, whereas amyloid of systemic amyloidosis (primary and multiple myeloma-associated) was negative. There was no difference between primary localized cutaneous amyloidosis (lichen amyloidosus and macular amyloidosis) and secondary localized cutaneous amyloidosis (amyloidosis associated with skin tumor). These results indicate that amyloid of localized cutaneous amyloidosis contains components derived from epidermal fibrous protein, probably tonofilaments of keratinocytes.

Amyloid↗
PubMedDate not supplied

Roles for state-level local health liaison officials in local public health surveillance and capacity building.

In 27 state health agencies, local health liaison units or officials (LHLOs) are formally assigned responsibility for fostering a close working relationship between the state health agency and local health departments (LHDs). Yet in most other states, other agency staff carry out these responsibilities informally. Even where formal LHLOs exist, the assigned functions and specific activities vary, with little consistency across states other than serving as a potential or, in most cases, a real and vital linkage between LHDs and the state agency. This linkage places the LHLO in a unique position to have extensive knowledge, data, and information on LHD activities and to play an important role in assessing and improving local public health practice. This report examines aspects of the LHLO-LHD relationship in terms of potential LHLO roles in LHD practice surveillance and capacity building. Surveys of LHLOs and LHDs indicate that both support the development of surveillance tools to measure LHD effectiveness as a means to enhance capacity building efforts. Although LHLOs may not know or have the specific information immediately available to assess local public health practice for LHDs in their state, they report being able to obtain the information if necessary and with sufficient time. Further, LHDs are willing to share information concerning local public health practice with their state health department, particularly with their state LHLO. These findings suggest that LHLOs could be extensively involved in surveillance strategies beyond merely collecting and aggregating information provided by LHDs.

Administrative Personnel↗
PubMed1976

The local anesthetic activity of saxitoxin alone and with vasoconstrictor and local anesthetic agents.

STX (saxitoxin), alone and with various vasoconstrictor and local anesthetic agents, was evaluated for its ability to produce topical anesthesia on the rabbit cornea, peripheral nerve block in the rat, and epidural anesthesia in the dog. High frequency and long duration of block can be attained if sufficiently high concentrations of STX are used, although latency is long and the doses used may produce systemic toxicity. Frequency of satisfactory blocks and mean duration of block can be increased and systemic toxicity reduced if STX is administered with a vasoconstrictor agent. Conventional local anesthetic agents also enhance the nerve blocking activity of STX. When appropriate concentrations of STX, vasoconstrictor and local anesthetic agents are used, systemic toxic effects are not manifested and the blocks produced exhibit the rapid onset and high frequency of block characteristic of the local anesthetic agent and the remarkably long duration of STX.

Anesthesia, Epidural↗
PubMed2002

Classifying local disease recurrences after breast conservation therapy based on location and histology: new primary tumors have more favorable outcomes than true local disease recurrences.

BACKGROUND: To distinguish true local recurrences (TR) from new primary tumors (NP) and to assess whether this distinction has prognostic value in patients who develop ipsilateral breast tumor recurrences (IBTR) after breast-conserving surgery and radiotherapy. METHODS: Between 1970 and 1994, 1339 patients underwent breast-conserving surgery at The University of Texas M. D. Anderson Cancer Center for ductal carcinoma in situ or invasive carcinoma. Of these patients, 139 (10.4%) had an IBTR as the first site of failure. For the 126 patients with clinical data available for retrospective review, we classified the IBTR as a TR if it was located within 3 cm of the primary tumor bed and was of the same histologic subtype. All other IBTRs were designated NP. RESULTS: Of the 126 patients, 48 (38%) patients were classified as NP and 78 (62%) as TR. Mean time to disease recurrence was 7.3 years for NP versus 5.6 years for TR (P = 0.0669). The patients with NP had improved 10-year rates of overall survival (NP 77% vs. TR 46%, P = 0.0002), cause-specific survival (NP 83% vs. TR 49%, P = 0.0001), and distant disease-free survival (NP 77% vs. TR 26%, P < 0.0001). Patients with NP more often developed contralateral breast carcinoma (10-year rate: NP 29% vs. TR 8%, P = 0.0043), but were less likely to develop a second local recurrence after salvage treatment of the first IBTR (NP 2% vs. TR 18%, P = 0.008). CONCLUSIONS: Patients with NP had significantly better survival rates than those with TR, but were more likely to develop contralateral breast carcinoma. Distinguishing new breast carcinomas from local disease recurrences may have importance in therapeutic decisions and chemoprevention strategies. This is because patients with new carcinomas had significantly lower rates of metastasis than those with local disease recurrence, but were more likely to develop contralateral breast carcinomas.

Actuarial Analysis↗
PubMed2005

Clinical outcome in patients with complete pathologic response (pT0) to preoperative irradiation/chemo-irradiation operated for locally advanced or locally recurrent rectal cancer.

BACKGROUND: The importance of pT0 stage after preoperative radiation/chemoradiation is unclear. METHODS: Four hundred and nineteen patients had preoperative irradiation (46-50 Gy/2 Gy fractions) for primary locally advanced (PLA) or locally recurrent (LR) rectal cancer. 141 PLA and 65 LR cases with R0 resections/M0 stage are studied. Two of the pT0 PLA patients had also been given sensitizing chemotherapy and two pT0 in the LR group had received pelvic hyperthermia as well. RESULTS: pT0 was achieved in 7% of 229 PLA and 8% of 190 LR patients. For the PLA group, actuarial 5-year survival of pT0 was 90% versus 53% for the pT > 0 group. The difference was statistically significant. At five years local recurrence was zero in pT0 patients versus 23% in pT > 0 (not significant). For the LR groups 5-year-survival was 62% for pT0 versus 45% for the other pT-stages, local recurrence was 17 and 35% respectively (not significant). The seemingly better results for pT0 cases of PLA cancers versus the LR ones did not reach statistical significance. CONCLUSION: pT0 after preoperative irradiation is associated with improved survival for pT0 cases of PLA. Our studies on pT0 LR was suggestive of an improvement in this group as well.

Adenocarcinoma↗
PubMed2005

Can pathological complete response in the primary tumour following pre-operative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for sterilisation of pelvic lymph nodes, a low risk of local recurrence and the appropriateness of local excision?

INTRODUCTION: Local excision is considered inappropriate treatment for T3-T4 rectal adenocarcinomas, as it cannot provide prognostic information regarding lymph node involvement and has a high risk of pelvic recurrence. Preoperative chemoradiation (CRT) studies in rectal cancer suggest that a pathological complete response (pCR) in the primary tumour provides an excellent long-term outcome. If downstaging to stage pT0 predicts a tumour response within the perirectal and pelvic lymph nodes, this may allow local excision to be performed without increased risk of pelvic recurrence. This retrospective study aimed to determine the incidence of involved lymph nodes following pCR (ypT0) after preoperative CRT and total mesorectal excision. METHOD: The outcome and treatment details of 211 patients undergoing preoperative CRT for clinically staged T3-T4 unresectable rectal adenocarcinomas between 1993 and 2003 at Mount Vernon Hospital were reviewed. RESULTS: Data were recorded from the 143 patients who completed treatment with a median follow-up of 25 months. Twenty-three patients (18%) were found to have had a pCR. Four out of 23 patients (17%) had involved lymph nodes. No pelvic recurrences developed after a ypCR. Overall survival was similar for patients with ypT0 or residual tumour. CONCLUSION: Pathological complete response in the primary tumour failed to predict a response in the perirectal lymph nodes (p=0.08). The degree of response predicted a lymph node response (p=0.02). The detection of ypCR identified patients with a low rate of pelvic recurrence. This may in the future allow selection of patients for whom local excision can be performed without a higher risk of local relapse.

Adenocarcinoma↗
PubMed1991

Results of external beam irradiation for rectal carcinomas locally recurrent after local excision or electrocoagulation.

The outcome of 42 patients who developed locally recurrent rectal carcinoma after initial local excision or electrocoagulation was presented. Five patients received combined surgery and radiotherapy (XRT). The remaining 37 patients were managed by XRT alone. The overall 5 year actuarial survival and local control rates were 21 and 22%, respectively. For patients who received XRT alone, the 5 year actuarial survival and local control rates were 20 and 15%, respectively. The corresponding figures were 35 and 40% for patients who received a total XRT dose of 50 Gy or more. One patient who underwent combined treatment developed rectal and bladder incontinence requiring surgery. For patients with rectal recurrence after initial conservative surgery, XRT is an alternative to abdominoperineal resection if major surgical resection is contraindicated.

Adult↗
PubMedDate not supplied

Nuclear localization signal-targeted poly(ethylene glycol) conjugates as potential carriers and nuclear localizing agents for carboplatin analogues.

Carboplatin is a low-molecular-weight anticancer drug that acts by binding to the nuclear DNA of cells. Thus, efficient delivery of the platinum drugs to the nucleus of the cancer cells may enhance the cytotoxicity of the drug. Efficient drug delivery to the nucleus of cancer cells requires three levels of localization: targeting to the cancerous tissue, accumulation in the cancer cells, and intracellular localization in the nucleus. Nuclear localization signals (NLS) are short positively charged basic peptides that actively transport large proteins across the nuclear membrane. We have prepared conjugates in which the NLS is tethered to poly(ethyleneglycol)carboplatin conjugate (NLS-PEG-Pt) and compared their pharmacological properties to those of their untargeted analogues that do not possess the NLS (PEG-Pt). NLS-PEG-Pt conjugates are rapidly internalized into cancer cells and accumulate in the nucleus. Despite their rapid nuclear localization, they form less Pt-DNA adducts than the untargeted analogues, PEG-Pt, and are also less cytotoxic. These results support the hypothesis that carboplatin (unlike cisplatin) may require cytosolic activation prior to its binding to nuclear DNA.

Active Transport, Cell Nucleus↗
PubMed1984

Sound localization in large mammals: localization of complex sounds by horses.

The idea that large mammals localize sounds more accurately than small mammals has been noted frequently and is usually explained by reference to their large interaural distance and the correspondingly broad binaural time (delta t) and spectral (delta fi) differences between their two ears. Sound-localization thresholds for single clicks and 100-ms noise bursts were determined for horses, and the magnitude of the binaural time (delta t) and spectral (delta fi) cues for sound direction were measured on a horse. Although horses have relatively large interaural distances and physically broad binaural-localization cues available to them, their sound direction thresholds were markedly poorer than those of other large mammals--averaging 22 degrees for noise and 30 degrees for clicks. It appears that sound-localization acuity is not determined simply by the physical availability of binaural cues.

Animals↗
PubMed1999

T-cell reaction to local anaesthetics: relationship to angioedema and urticaria after subcutaneous application--patch testing and LTT in patients with adverse reaction to local anaesthetics.

BACKGROUND: Local anaesthetics are known to elicit T-cell reactions after epicutaneous application, namely contact dermatitis. In addition, adverse reactions like urticaria and angioedema are rather common after submucosal or subcutaneous injection. The pathogenesis of these side-effects, which appear frequently hours after application, is unknown, but thought to be not immunoglobulin E-mediated, since immediate skin tests are mostly negative. OBJECTIVES: We investigated whether patients who developed urticaria and angioedema after subcutaneous application have a T-cell sensitization to local anaesthetics, which might be responsible for the symptoms. METHODS: Twenty patients with generalized and/or local cutaneous reactions after LA were examined with intradermal testing using a standard panel of six LAs and patch testing using between seven and nine LAs in vaseline and four LAs in PBS. In 10 patients, a lymphocyte transformation test (LTT) was performed. RESULTS: Only 2/20 patients had an immediate skin reaction (positive intradermal test), whereas 6/20 patients had a positive delayed skin reaction (positive patch test). In 6/10 subjects the LTT was positive. CONCLUSIONS: Delayed appearance of urticaria and angioedema after subcutaneous application of local anaesthetics may be related to a T cell- mediated sensitization, which might be detected by patch testing or LTT.

Adolescent↗