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At least 19 recordsLinked to original sources
PubMed2024

Tumor specimen cold ischemia time impacts molecular cancer drug target discovery.

Tumor tissue collections are used to uncover pathways associated with disease outcomes that can also serve as targets for cancer treatment, ideally by comparing the molecular properties of cancer tissues to matching normal tissues. The quality of such collections determines the value of the data and information generated from their analyses including expression and modifications of nucleic acids and proteins. These biomolecules are dysregulated upon ischemia and decompose once the living cells start to decay into inanimate matter. Therefore, ischemia time before final tissue preservation is the most important determinant of the quality of a tissue collection. Here we show the impact of ischemia time on tumor and matching adjacent normal tissue samples for mRNAs in 1664, proteins in 1818, and phosphosites in 1800 cases (tumor and matching normal samples) of four solid tumor types (CRC, HCC, LUAD, and LUSC NSCLC subtypes). In CRC, ischemia times exceeding 15 min impacted 12.5% (mRNA), 25% (protein), and 50% (phosphosites) of differentially expressed molecules in tumor versus normal tissues. This hypoxia- and decay-induced dysregulation increased with longer ischemia times and was observed across tumor types. Interestingly, the proteomics analysis revealed that specimen ischemia time above 15 min is mostly associated with a dysregulation of proteins in the immune-response pathway and less so with metabolic processes. We conclude that ischemia time is a crucial quality parameter for tissue collections used for target discovery and validation in cancer research.

Humans↗
PubMed2026

Spatiotemporal transcriptomic analysis during cold ischemic injury to the murine kidney reveals compartment-specific changes.

BACKGROUND: Kidney transplantation is the preferred treatment strategy for end-stage kidney disease. Deceased donor kidneys usually undergo cold storage until kidney transplantation, leading to cold ischemia injury that may contribute to poor graft outcomes. However, the molecular characterization of potential mechanisms of cold ischemia injury remains incomplete. RESULTS: To bridge this knowledge gap, we leverage 10x Visium spatial transcriptomic technology to perform full transcriptome profiling of murine kidneys subject to varying durations of cold ischemia typical in a deceased donor kidney transplant setting. We develop a computational workflow to identify and compare spatiotemporal transcriptomic changes that accompany the injury pathophysiology in a tissue compartment-specific manner. We identify proportional enrichment of oxidative phosphorylation (OXPHOS) genes with increasing duration of cold ischemia injury within the oxygen-lean inner medulla region, suggestive of atypical metabolic presentation. This is distinct in cold ischemia injury tissue compared to warm ischemia-reperfusion kidney injury tissue. Spatiotemporal trends are validated by qPCR and immunofluorescence in a larger cohort of mice. CONCLUSIONS: Altogether, our spatiotemporal transcriptomic analysis identifies coordinated molecular changes within metabolic pathways such as OXPHOS deep within the cold ischemic kidney, highlighting the need for increased attention to the inner medulla and potential opportunities for new insights beyond those available from superficial biopsy-focused tissue examination.

Animals↗
PubMed1978

Intrarenal hemodynamics in the transplanted rat kidney.

Regional and single glomerular blood flow conditions in the transplanted rat kidney after various periods of cold ischemia were investigated with use of the microsphere method. Intravascular injection of a silicon rubber compound (Microfil) allowed identification and sampling of single glomeruli. The periods of ischemia were two hours (minor damage), 12 hr (intermediate damage), and 16 hr (severe damage). After two hours of cold ischemia, the regional and total renal blood flows were fairly normal. After 12 hr and 16 hr of cold ischemia, the total and regional blood flows were reduced five minutes after recirculation, the reduction being pronounced in the deep cortex and juxtamedullary glomeruli. In the 12-hr group, the blood flow showed complete restitution after 65 min, whereas in the 16-hr group, the blood flow in the inner cortex and juxtamedullary glomeruli remained decreased. An impairment of medullary circulation would seem to be an important component in the pathophysiology of acute renal failure in this model.

Animals↗
PubMed1978

Nephron function of the transplanted rat kidney.

Tubular function in the early phase (one to three hours) after transplantation of rat kidneys was analyzed with respect to glomerular filtration, vascular and tubular pressures, and excretory variables. Kidneys exposed to a short period of cold ischemia (two hours) functioned almost normally, except for a polyuria. After 12 and 16 hr of cold ischemia, nephron heterogeneity appeared with 1) "normal" tubules, 2) dilated tubules, and 3) collapsed tubules. In the "normal" tubules, the pressure was increased to 20 mm Hg, and the filtration was reduced in proportion to the mean net driving force. The dilated tubules had no filtration due to a more or less complete tubular obstruction, probably located in the thin loop of Henle and in the collecting ducts. The collapsed tubules had no filtration due to glomerular ischemia, which in turn might be the consequence of afferent arteriolar constriction. The total GFR was greatly reduced since only the "normal" tubules contributed to the total filtration. Concentrating ability and potassium secretion were also impaired. We interpreted this impairment as being due to medullary dysfunction, which would explain the isosthenuria and the impaired potassium transport.

Animals↗
PubMed1979

[Renal hypothermia in situ. Comparison between surface and perfusion cooling concerning renal function in pigs (author's transl)].

There are 2 competing methods for cooling the kidney in situ during surgical ischemia: from without by applying ice to the renal surface and from within by perfusing the renal artery. The latter procedure is said to be superior in protecting renal function. Herein the protective effect on renal function of both methods are compared. Pigs of 15--25 kg weight underwent nephrectomy on one side. The remaining kidney was subjected to cold ischemia during 90 minutes while perfusion- or surface cooling was performed. For perfusion cooling the aorta was punctured and the catheter introduced into the renal artery. The perfusing liquid consisted of a physiologic electrolyt solution (Ringer-Lactate) with heparin kept at a temperature of 3--5 degrees C. The initial perfusion lasted 10 minutes and resulted in a median renal core temperature of 23 degrees C. Then the kidney was put on a cooling pad and every 15 minutes again perfused for one minute. For surface cooling sterile melting ice made of glucose solution 5% was applied directly to the kidney. The renal core temperature could be kept at 15--20 degrees C. The two methods of hypothermia were judged by comparing the serum creatinine levels and the I131-hippuran clearances one month after surgery. There was no difference whatever as analysed by the t-test. Hypothermia by applying ice to the renal surface therefore proved to be equivalent to hypothermia by perfusion. Moreover it is much simpler.

Animals↗
PubMed1977

Pretreatment of cadaver donors with methylprednisolone in human renal allografts.

Fifty cadaveric kidney donors were randomly allocated to two groups. Group 1 received 5 grams of intravenously administered methylprednisolone two to four hours prior to organ harvesting after the pronouncement of brain death. Group 2, which served as the control group, received no pretreatment. Of 100 kidneys harvested, 16 were discarded for various reasons, and 84 were transplanted and were available for evaluation, 40 from the pretreatment group and 44 from the control group. The transplant centers using these kidneys were unaware of the status of the kidney they received, that is, whether it was from a pretreated or a control group. The two groups of kidneys, pretreated and control, did not differ according to the length of warm or cold ischemia time or presence of preformed cytotoxic antibodies. The difference in graft failure between the two groups at three months was insignificant, even when the two groups were compared according to the method of preservation used.

Antibody Formation↗
PubMed1977

The influence of 13 clinical and immunological factors on renal graft survival: a contingency table analysis.

A statistical method which accounts for the heterogeneity of clinical materials is presented and applied to a material of necrokidney transplantations. It is concluded that the recipient sex and the period in which the transplantation was performed are the most important factors (best prognosis for female recipients, best programs for transplantations in the first periods) and that the HLA-match grade has a significant influence on graft survival for male recipients and transplantations with short cold ischemia time. The present analysis has furthermore demonstrate the heterogeneity of the material as judged by the associations between factors and the overestimation of the influence of some of the factors by direct comparisons.

ABO Blood-Group System↗
PubMedDate not supplied

[Organization and results of cadaver kidney transplantation from 1969 to 1973 (author's transl)].

France transplant was founded in order to organize rationally the cadaver kidneys transport and transplantation with is omogenous compatibility tests. 2143 hemodialysis patients have been presently (1-9-72) treated in 82 dialysis center in France; 964 of them are in the France Transplant waiting list. According with recent laws, nervous function cessation is synonimous of death. That made possible, by good resuscitation techniques, to maintain a good level of circulation and oxigenation of organs. Family permit is required for this purpose. 17 medical transporttion staffs are at work in 12 France towns and cooperate with 12 typing laboratoires working with the same techniques and reagents. One permanent secretariat in Paris is always telex connected with all staffs and mantains a continuous up to date patients waiting list. 415 cadaver kidneys were transplanted, 255 in the same town and 160 trabsported from a town another. A significative rise in cold ischemia times happened recently because of the increasing number of transported kidneys.

Cadaver↗
PubMed1979

Forearm arterial injuries.

The effects of single forearm arterial injuries with and without associated neurological injuries were studied. Fifty subjects were evaluated: seven patients with isolated arterial lacerations, 15 patients with isolated nerve lacerations, 13 patients with combined nerve and arterial injuries, and 15 control subjects. A series of noninvasive peripheral vascular studies were correlated with the symptoms produced by a controlled cold-environment exposure. The hemodynamic alterations associated with symptoms of hand ischemia, and particularly with cold intolerance, were studied. Unrepaired single arterial injuries caused modest, consistent alterations in hand vascularity, but few signs of ischemia or symptoms of cold intolerance. The remaining intact artery demonstrated a consistent increase in flow velocity. Combined nerve and artery injuries caused the most significant alterations in hand vascularity, and median nerve and associated artery injuries caused the most disabling symptoms. Single arterial lacerations had no effect on the rate or completeness of recovery from associated nerve injuries.

Arteries↗
PubMed1978

Preliminary experience with the pH-triggered pacemaker.

A cardiac pacemaker capable of responding to blood acidosis by change in its stimulation rate allows adjustment to a patient's metabolic needs. The blood pH is sensed by an iridium oxide electrode in the right atrium. During exercise, the venous pH decreases and the paced ventricular rate increases. If acidosis persists, the paced rate gradually returns to baseline and reaches it after about 70 minutes. A pH-triggered pacemaker has been implanted in a 72-year-old male. The pacemaker remained responsive one year after implant, increasing rate during exercise, cold pressor stress, ischemia of the arms and emotional stress.

Aged↗
PubMed1978

Endorphins: naloxone fails to alter experimental pain or mood in humans.

In 30 human subjects, experimental pain was produced by either ischemia or cold-water immersion. In a double-blind procedure, intravenous doses of up to 10 milligrams of naloxone hydrochloride in saline were indistinguishable from similarly administered saline alone. There were no effects on subjective pain ratings, finger plethysmograph recordings, or responses to mood-state questionnaires. These laboratory procedures do not activate any functionally significant pain-attenuating or mood-altering effect of endorphins.

Clinical Trials as Topic↗
PubMed1977

Twenty-four hour canine renal preservation by pulsatile perfusion, hypothermic storage, and combinations of the two methods.

A comparison of the effectiveness of two renal preservation techniques was studied in 30 cannine renal pairs. In the absence of warm ischemia, 24-hr preservation by pulsatile perfusion was not significantly superior to hypothermic storage. When 15 min of warm ischemia was added as an additional insult, pulsatile perfusion afforded significantly better early function than cold storage. Combinations of pulsatile perfusion and hypothermic storage following 15 min of warm ischemia were superior to hypothermic storage alone, but inferior to pulsatile perfusion. Kidneys initially perfused for 6 hr and then cold-stored functioned slightly better than kidneys perfused for 18 hr after initial cold storage.

Animals↗
PubMed1979

Raynaud's phenomenon: primary and secondary causes.

The terms "Raynaud's disease" and "Raynaud's phenomenon" are often used interchangeably, as if they were a single problem. Because prognosis and therapy are different with each of these entities, 86 patients with episodic digit ischemia were evaluated over the past five years. All patients were evaluated similarly with plethysmography, angiography, and other studies for underlying causes of the digital ischemia. From the study, it was concluded that the majority of the patients had an underlying cause for the problem even though they satisfied the commonly accepted criteria for the diagnosis of Raynaud's disease. It is clear that the diagnosis of Raynaud's disease must be one of exclusion, because it is more uncommon than is generally appreciated by the medical community.

Cold Temperature↗