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At least 109 records · Page 6Linked to original sources
PubMed2002

A system for breast implant selection based on patient tissue characteristics and implant-soft tissue dynamics.

Primary breast augmentation patients have widely varying characteristics of their breast envelope, parenchyma, and adjacent tissues. When preoperative breast implant selection does not specifically address critical soft-tissue parameters individual to each patient, risks of complications increase. Complications that occur from failure to reconcile a patient's wishes for breast size with her individual tissue characteristics include skin stretch and thinning, ptosis, atrophy of parenchyma, implant edge or shell visibility, implant edge or shell palpability, visible traction rippling, "bottoming" deformities, and lateral implant displacement with widening of the intermammary distance. Previous dimensional systems address implant parenchyma base width relative to implant base width, but no published system adequately addresses or attempts to quantitate the third dimension, tissue stretch, that is critical to estimate amount of fill necessary in a wide range of breast and tissue types. This system addresses the tissue characteristics (T) of the envelope (E), the parenchyma (P), and the implant (I), and the dynamics (D) of implant and filler distribution that affect soft tissues. The acronym TEPID summarizes the key factors that determine aesthetic results and occurrence of problems and reoperations following breast augmentation. This simple, efficient, and clinically practical system focuses on only three tissue measurements to estimate implant volume required to fill each patient's existing breast envelope, on the basis of her individual tissue characteristics: base width of the parenchyma, anterior pull skin stretch, and areola- and/or nipple-to-inframammary-fold distance measured under maximal stretch. The surgeon then adjusts initial volume to address differences in degree of skin stretch (anterior pull skin stretch) and contribution of the patient's existing parenchyma to stretched envelope fill, and to address differences in implant dimensions and filler distribution dynamics. To base decisions of implant pocket location on quantifiable soft-tissue coverage thickness, the system measures soft-tissue pinch thickness of the upper pole and at the inframammary fold. Surgeon time required to measure, estimate, and make preoperative implant selection decisions is less than 5 minutes. This system evolved from compiling and reviewing measurements and results from 330 primary breast augmentations from 1996 to 1999, including round and anatomic implant types with smooth shells and two different textured shells. The TEPID system was then used concurrently with the previous dimensional system for patient tissue evaluation and preoperative implant selection in 627 consecutive primary augmentation cases over a 3-year period from January of 1998 to January of 2001. Implant selection that did not comply with the parameters of the system was necessary in only eight cases. The TEPID system is a simple, efficient, and clinically practical method that allows surgeons to base implant selection on clinically quantifiable, individual patient tissue characteristics.

Adult↗
PubMed1991

Human colon cancer tissues are more sensitive than rectal cancer tissues to antitumor drugs in vitro.

The chemosensitivities of 62 human colon cancer tissues, 67 rectal cancer tissues and 31 tumor-adjacent normal mucosal tissues were determined using the in vitro succinate dehydrogenase inhibition (SDI) test. These tissues obtained at the time of surgery were exposed to carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cisplatin (DDP) and 5-fluorouracil (5-FU). The chemosensitivity was considered as positive when succinate dehydrogenase (SD) activity of the drug-treated cells decreased to below 50% of that of control cells, on day 3 of exposure. Decrease in the SD activity was noted in the colon cancer tissues, compared to the rectal cancer tissues, exposed to six antitumor drugs and in particular, to CQ (p less than 0.05), DDP (p less than 0.01) and ACR (p less than 0.05, one-sided paired t test). Decrease in the SD activity was noted in the tumor tissues, compared to the tumor-adjacent normal tissues, exposed to CQ, MMC and ACR (p less than 0.01). The sensitive rates were higher in the colon cancer tissues than the rectal cancer tissues, against all six antitumor drugs. Our findings show that the rectal cancer tissues are resistant to antitumor drugs, compared to the colon cancer tissues in vitro. When selecting antitumor drugs to treat patients with a rectal cancer, the assessment for chemosensitivity of the related tissues is crucial.

Antineoplastic Agents↗
PubMed2000

Tissue restoration, tissue engineering and regenerative medicine.

Recently, thanks to the rapid progress of new technologies in cell modulation, extracellular matrix fabrication and synthetic polymers mimicking bodily structures, the self-regeneration of bodily defects by host tissue has been considered by many researchers. The conventional science of art in biomaterials has been concerned with restoring damaged tissue using non-biological materials such as metals, ceramics and synthetic polymers. To overcome the limitations of using such non-viable materials, several attempts to construct artificial organs mimicking natural tissue by combining modulated cells with extracellular matrix-hybridized synthetic polymers have produced many worthy results with biologically functioning artificial tissues. The process involved in manufacturing biomaterials mimicking living tissue is generally called tissue engineering. However recently, the extension of knowledge about cell biology and embryology has naturally moved the focus from tissue restoration to tissue regeneration. Especially, embryonic and mesenchymal stem cells are attractive resources due to their potential for the differentiation of various tissue cells in response to signal transduction mediated by cytokines. Although no one knows yet what is the exact factor responsible for a stem cell's ability to differentiate between specific cells to generate specific tissue, what has been agreed is that delivering stem cells into the body provides a strong potential for the regeneration of tissue. In this review, the historical issues and future possibilities involved in medical tissue restoration and tissue regeneration are discussed.

Animals↗
PubMed1990

[Effects of alpha-human ANF and angiotensin II on aldosterone secretion in vitro from cultured human adrenal tissues and APA tissues].

The effects of the alpha-human ANF and angiotension II on aldosterone secretion in vitro from cultured human adrenal tissues and the aldosterone-producing adenoma (APA) tissues were studied. The fresh human normal adrenal and APA tissues were obtained surgically from five patients. The tissues were mined 1.0 mm3 with scissors, put in DMEM containing 0.25% trypsin, and digested at 37 degrees C for 10 min. Then the tissues were washed with DMEM. The tissues were incubated in 4 ml DMEM containing 10% fetal calf serum at 37 degrees C under 5% CO2 in air for seven days and the aldosterone levels of the culture medium were determined by radioimmunoassay (RIA). The experiments were started on the tenth to fiftieth day of culture. The results show that the effect of alpha-human ANF (10(-8) mol/L final concentration) on aldosterone secretion from normal adrenal tissues was increased at 30 min following a decrement, but do not inhibit the aldosterone secretion in APA tissues. The aldosterone of short duration was inhibit by alpha-human ANF (3 x 10(-8) mol/L or 5 x 10(-8) mol/L) and the aldosterone secretion in a dose-dependent manner in the adenoma tissues. The aldosterone responses were not stimulated by angiotensin II (10(-9) mol/L) in normal adrenal and adenoma tissues, but angiotensin II (5 x 10(-9) mol/L) can stimulate APA tissues. Our results indicate the lack of effect of alpha-human ANF and angiotensin II on APA tissues could be due to the absence of receptors or a variance of the receptors, and/or the enzymes of steroidogenesis were abnormal. These tissues had a marked aldosterone response to ANF and angiotensin II during culturing in one month.

Adenoma↗
PubMed1998

Characterization of tissue morphology, angiogenesis, and temperature in the adaptive response of muscle tissue to chronic heating.

Previous investigations on the in vivo effects of chronic heat on tissue suggest a response whereby heated tissue temperatures decrease over time. This response occurred in conjunction with localized angiogenesis, which possibly contributed to the temperature decreases by increasing local perfusion and enhancing tissue heat transfer. Our own studies were the first to use a chronic heat source to heat tissue at initial interfacial temperatures between 40 degrees C and 46 degrees C. Initial temperatures above 45.3+/-2.2 degrees C caused necrosis of adjacent tissue. Through an adaptive response, the necrosis was removed by 7 weeks and replaced by a highly vascularized tissue capsule at 41.8+/-0.5 degrees C. The present study sought to characterize the spatial distribution, number of capillaries, and temperatures associated with this adaptive response. Heated and control muscle tissue sections were removed after 2, 4, and 7 weeks of heating at 0.08 W/cm2. Tissue layer thicknesses and capillary densities were measured and correlated with corresponding tissue temperatures. Necrosis was present adjacent to the heat source at 2 and 4 weeks; however by 7 weeks, a highly vascularized fibrous tissue capsule had replaced nearly all necrosis. Capillary densities, particularly near the heat source, were significantly greater at 7 weeks than at either 2 or 4 weeks. Capillary densities in heated tissue capillary fronts tripled from 2 to 7 weeks (106.4+/-14.3 caps/mm2 versus 39.1+/-18.5 caps/mm2). Furthermore, a mean temperature of 41.7+/-0.9 degrees C was measured in heated tissue capillary fronts at all durations, suggesting that this may be a threshold temperature for heat-induced angiogenesis or endothelial cell survival. These findings more completely characterize the perfusion component of the current mathematical model for heat transfer in tissue and will help to establish guidelines for the functional heat loss that an implantable, heat-producing device may allow.

Acclimatization↗
PubMed1993

Plasminogen activators and plasminogen activator inhibitors in connective tissues and connective tissue cells: influence of the neuropeptide substance P on expression.

Tissue segments isolated from ligament, epiligament, and synovial tissues from mature female New Zealand White Rabbits were demonstrated to constitutively secrete a plasminogen activator. Several tissues were also observed to constitutively secrete a plasminogen activator inhibitor which was detected in the form of a PA-PAI complex. Heterogeneity was observed in PA and PAI activity between the different connective tissues. Heterogeneity also existed between and within the medial collateral (MCL), lateral collateral (LCL), and the anterior cruciate (ACL) ligaments. In addition to the differences in constitutive expression of PA and PAI activity, differences in the responsiveness to the neuropeptide substance P (10(-5)-10(-9) M) were also detected. This responsiveness to substance P was displayed by an increase in PA and PAI activity in the conditioned medium. The pattern of responsiveness reflected the degree of innervation of these tissues. That is, synovium and epiligament tissue were the most responsive tissues to substance P while the MCL, LCL and ACL were less responsive to the neuropeptide. Parallel results were obtained using cell culture with fibroblasts isolated from the above mentioned tissues. That is, the pattern of responsiveness was similar between cells and tissue segments. More specifically, cells isolated from both synovium and epiligament increased their both their PA (slightly) and PAI activity following exposure to substance P. This was demonstrated at both the protein and RNA level. Thus, cells within a tissue maintain their phenotype when removed from their three-dimensional matrix. These results are unique in demonstrating that normal ligament and synovial cells and tissue respond to substance P by altering the expression of PA and PAI activity. This investigation further supports the concept that innervation may be important in normal connective tissue function.

Animals↗
PubMed2005

Tissue distribution and bioconcentration factors of PCDD/Fs in the liver and adipose tissue following chronic ingestion of contaminated milk in rats.

The aim of this study was to determine the tissue distribution of 17 PCDD/Fs following the chronic ingestion of contaminated milk in rats and to assess the "target tissue/milk" BioConcentration Factors (BCFs) of these molecules. Contaminated milk, collected in a polluted area, has been incorporated into the diet of male rats at a low dose (31 pg I-TEQ/day/rat). For this exposure, the accumulation of PCDD/Fs in target tissues (liver and adipose tissue) was limited, the tissue concentrations stabilising between 90 and 120 days of daily intake to levels close to 3 pg/g of tissue (all tissues and molecules combined). The tissue distribution seemed to be governed by the congeners properties and by the tissue characteristics. An increase in the chlorination degree of dioxins caused a decrease in their incorporation in the adipose tissue, and consequently of the BCF values. Moreover, the distribution of dioxins between hepatocytes and adipocytes differed: unlike the liver, the quantities of dioxins in the adipose tissue were significantly (P<0.05) correlated to the quantity of tissue fat. Only in the liver, the incorporation of PCDDs seemed to be facilitated when the chlorination degree of these congeners increased, the reverse phenomenon having been observed for PCDFs. However, for the same level of chlorination, the BCFs of PCDFs were 2.4 times higher than those of PCDDs in this tissue. The absence of correlation between the quantity of dioxins and that of fat and the BCFs differences of theses congeners suggested that dioxins fixation process in the liver was selective.

Adipose Tissue↗
PubMed1989

Ontogenetical changes in adipose tissue of the cat: convertible adipose tissue.

The ultrastructural characteristics of the inguinal, interscapular, and perirenal adipose tissue in kittens and cats were studied. There were no qualitative differences among adipocytes in the three anatomical areas. The only recorded difference was in the amount of lipids stored in the adipocytes in younger stages. Immediately after birth lipids occupied 25% of the volume in the inguinal area, 15% in interscapular fat tissue, and 10% in perirenal fat tissue. At this stage the adipose tissue morphologically resembled brown adipose tissue (BAT) of rodents. Two weeks after birth, lipids accumulated and adipocytes in the inguinal area became unilocular and appeared similar to white adipose tissue (WAT). A similar transition occurred approx 25 days after birth in interscapular fat and approx 6 weeks after birth in the perirenal area. No morphological signs of any cell degradation or destruction, nor any increased activity of preadipocytes, were seen during this conversion from BAT-like to WAT-like adipose tissue. The conversion of the adipose tissue was correlated with a decrease in vascularization and innervation, a loss of intercellular connections, and a changed mitochondrial population. Mitochondria in multilocular adipocytes resembled those in typical BAT which contain uncoupling protein ("UC-mitochondria"). After conversion to unilocular adipocytes the amount of mitochondria was halved, their cristae even more reduced, and their appearance was of a WAT-type (UCP-lacking mitochondria, which are coupled under physiological conditions; "C-mitochondria"). Since this category of adipose tissue differs from both typical brown and white adipose tissue, the name "convertible adipose tissue" (CAT) is proposed. Apparently adipose tissue from comparatively large mammals is of this convertible type.

Adipose Tissue↗
PubMed1991

Blood content in guinea-pig tissues: correction for the study of drug tissue distribution.

The blood content in different organs or tissues of guinea-pigs was determined by means of [125I]bovine serum albumin. The blood distribution expressed as percentage of total body blood for various organs or tissues ranged from 0.35 (adipose) to 17.5 (muscle)%. The blood content in tissue preparations expressed as the blood background correction factor, F (ml blood/g wet tissue) depended on the extent of bleeding during experiment; that factor can cause a considerable difference in the results of a tissue distribution study of a drug. Blood content was high in the lung (0.36 ml/g), heart, liver, kidney and spleen, but low in adipose and brain tissues (0.021 ml/g). The distribution of valproic acid in various tissues of guinea-pigs after intravenous injection was determined from the homogenates of isolated organs. The results showed that blood contamination can greatly alter the data of tissue distribution of a drug to as much as 25%. This study proposed a maximum (non-bled) and a minimum (extreme-bled) blood background correction factor for respective tissues of guinea-pigs, as well as equations for correcting the blood contamination in tissue during the drug distribution study. The results suggest that to obtain an exact analysis of drug concentrations in specific tissues, a correction for the blood of that specific tissue is necessary.

Animals↗
PubMed2004

New perspectives on bioengineering of joint tissues: joint adaptation creates a moving target for engineering replacement tissues.

The current paradigm in tissue engineering is that "full regeneration" or "total replacement" of normal tissue is required in order to restore joint function. However, there is considerable evidence that suggests that targets other than "normality" may actually be required for tissue substitutes. Sometimes "less than normal" tissue properties of substitutes may be required following an injury, and sometimes "more than normal" may be required (following tissue degradation, damage, and failure). Diarthrodial joints function as "organs" in a physiological sense and normal individual joint tissues work together to share the mechanical requirements demanded by internal and external forces. Each tissue has some genetic and biological ability to adapt and/or remodel, to accommodate to the changing biomechanical needs invoked by injury and each tissue changes with age. This dynamic genetic and environmentally driven situation affecting the (uninjured) tissues in both injured and uninjured joints suggests that there is a "moving target" for bioengineered replacement tissues. After degeneration, damage, and failure of adaptation of other joint components, the mechanical requirements of replacement tissues likely increases dramatically beyond those of their normal counterparts. These concepts have important implications to designs of tissue bioengineering experiments and to their mechanical targets.

Adaptation, Physiological↗
PubMed1969

Clearing-factor lipase in adipose tissue. Distinction of different states of the enzyme and the possible role of the fat cell in the maintenance of tissue activity.

1. Incubation of intact epididymal adipose tissue from fed rats at 37 degrees in an albumin solution at pH7.4 in vitro results in rapid loss of clearing-factor lipase activity until a low activity, stable to prolonged incubation, is attained. The clearing-factor lipase activity of intact tissue from starved rats, which is initially much less than that of tissue from fed rats, is mainly stable to incubation at 37 degrees . 2. Much of the clearing-factor lipase activity of intact epididymal adipose tissue from fed rats is inactivated by collagenase. The enzyme activity of intact tissue from starved rats is not inactivated by collagenase. 3. The clearing-factor lipase activity of fat cells isolated from the epididymal adipose tissue of fed rats is stable to prolonged incubation at 37 degrees . It represents only a small proportion of the total activity of the intact tissue. In starved rats, the isolated fat cells contain a much higher proportion of the activity of the intact tissue. Their activity is also stable at 37 degrees . 4. Incubation of isolated fat cells in a serum-based medium leads to a progressive rise in clearing-factor lipase activity. Actinomycin increases the extent of this rise in activity. No rise in clearing-factor lipase activity occurs when stromal-vascular cells isolated from epididymal adipose tissue are incubated in the medium. 5. The findings indicate that less than 20% of the activity of intact adipose tissue from fed rats is retained when fat cells are isolated from the tissue by collagenase treatment. The activity that is lost could be that which normally functions in the uptake of triglyceride fatty acids by the tissue.

Adipose Tissue↗
PubMed2003

Intralumenal tissue-engineered therapeutic stent using endothelial progenitor cell-inoculated hybrid tissue and in vitro performance.

Rapid reendothelialization at an atherosclerotic lesion after balloon or stent inflation may be essential for maintaining homeostatic tissue function, which could reduce or prevent restenosis. We devised an endothelial progenitor cell (EPC)-enriched tubular hybrid tissue and mounted it on a small-diameter metallic stent (outer diameter, 1.5 mm), which is used for intravascular angioplasty to atherosclerotic lesions. This study addressed the fabrication technique and in vitro performance to verify lumenal endothelialization. A thin collagenous tubular tissue was prepared by contraction of collagen fibers by inoculated EPCs, which were isolated from canine peripheral blood and expanded ex vivo, in a collagen gel formed in a mold. An EPC-inoculated hybrid tissue-covered stent, loaded on a balloon catheter, was inserted into a tubular hybrid vascular medial tissue inoculated with smooth muscle cells (SMCs) as an arterial media mimic, and subjected to balloon inflation for enlargement (outer diameter, 3 mm), followed by balloon deflation. The EPC-inoculated hybrid tissue-covered stent tightly adhered to the lumenal surface of the hybrid medial tissue. On culture, EPCs in the hybrid tissue migrated and proliferated to form a completely endothelialized lumenal surface at stented sites as well as sites adjacent to the vascular hybrid medial tissue with the prolongation of culture. This in vitro pilot study before in vivo experiments suggests that an EPC-inoculated hybrid tissue-covered stent may be a novel therapeutic device for reendothelialization or paving with EPC-enriched tissue at an atherosclerotic arterial wall, resulting in the prevention of restenosis and the rapid formation of normal tissue.

Animals↗
PubMed1997

Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue.

Family 1 UDP-glucuronosyltransferases (UGTs) (UGT1A) are encoded by a locus that predicts the existence of at least nine individual proteins. The different proteins are generated by exon-sharing, which results in the production of a family of proteins that contain identical, 245-amino acid, carboxyl-terminal domains and an amino-terminal region of approximately 280 amino acids. The diversity of the UGT1A locus suggests the existence of complex regulation, most likely designed to account for the variable and specific glucuronidation requirements. However, the tissue-specific and extrahepatic regulation of the complete UGT1A locus has not been defined to date. In this study, quantitative duplex reverse transcription-polymerase chain reaction was used to analyze UGT1A RNA expression in 16 hepatic, four biliary, and two gastric human tissue specimens. UGT1A3 and UGT1A6 were found to be expressed in the three tissues, whereas UGT1A5 and UGT1A8 were not expressed. Hepatocellular and biliary tissue expressed UGT1A1 and UGT1A4 but hepatocellular tissue uniquely expressed UGT1A9, whereas biliary tissue expressed UGT1A10. In contrast to hepatocellular tissue, gastric tissue expressed UGT1A7 in addition to UGT1A10. The expression of UGT1A9 in hepatic tissue, UGT1A7 in gastric tissue, and UGT1A10 in biliary and gastric tissue provides evidence for the selective regulation of the UGT1A locus in hepatic and extrahepatic tissues. The newly identified UGT1A7 and UGT1A10 transcripts were cloned and found to be 95.86% identical. Sequence analysis confirmed two proteins with divergent amino termini of 285 residues and identical carboxyl termini of 245 residues. This study provides evidence for hepatic and extrahepatic regulation of the human UGT1A locus and identifies two novel extrahepatic transcripts of the UGT1A family.

Alternative Splicing↗
PubMed2005

The development of common data elements for a multi-institute prostate cancer tissue bank: the Cooperative Prostate Cancer Tissue Resource (CPCTR) experience.

BACKGROUND: The Cooperative Prostate Cancer Tissue Resource (CPCTR) is a consortium of four geographically dispersed institutions that are funded by the U.S. National Cancer Institute (NCI) to provide clinically annotated prostate cancer tissue samples to researchers. To facilitate this effort, it was critical to arrive at agreed upon common data elements (CDEs) that could be used to collect demographic, pathologic, treatment and clinical outcome data. METHODS: The CPCTR investigators convened a CDE curation subcommittee to develop and implement CDEs for the annotation of collected prostate tissues. The draft CDEs were refined and progressively annotated to make them ISO 11179 compliant. The CDEs were implemented in the CPCTR database and tested using software query tools developed by the investigators. RESULTS: By collaborative consensus the CPCTR CDE subcommittee developed 145 data elements to annotate the tissue samples collected. These included for each case: 1) demographic data, 2) clinical history, 3) pathology specimen level elements to describe the staging, grading and other characteristics of individual surgical pathology cases, 4) tissue block level annotation critical to managing a virtual inventory of cases and facilitating case selection, and 5) clinical outcome data including treatment, recurrence and vital status. These elements have been used successfully to respond to over 60 requests by end-users for tissue, including paraffin blocks from cases with 5 to 10 years of follow up, tissue microarrays (TMAs), as well as frozen tissue collected prospectively for genomic profiling and genetic studies. The CPCTR CDEs have been fully implemented in two major tissue banks and have been shared with dozens of other tissue banking efforts. CONCLUSION: The freely available CDEs developed by the CPCTR are robust, based on "best practices" for tissue resources, and are ISO 11179 compliant. The process for CDE development described in this manuscript provides a framework model for other organ sites and has been used as a model for breast and melanoma tissue banking efforts.

Computational Biology↗
PubMed2001

AmpFlSTR Profiler Plus and AmpFlSTR COfiler analysis of tissues stored in GenoFix, a new tissue preservation solution for mass disaster DNA identification.

A preliminary study was conducted to assess the capability of a new alcohol-based tissue fixative, GenoFix, to preserve DNA from biopsy tissues stored at room temperature and/or -20 degrees C in a freezer, for subsequent short tandem repeat (STR) DNA typing analysis. Fresh human smooth muscle samples were stored at room temperature in GenoFix for one month and up to one year and seven months before being processed using the megaplex STR systems, AmpFlSTR Profiler Plus and AmpFlSTR COfiler. Alternatively, muscle tissues in GenoFix were placed at -20 degrees C in a freezer for up to 3 1/2 years following two to three months in the fixative at room temperature. DNA analysis was also carried out on tissues stored in GenoFix for one month at room temperature and subsequently paraffin-embedded and stored at room temperature for four years. The AmpFlSTR Profiler Plus and AmpFlSTR COfiler STR profiles produced, using DNA extracted from all fixed tissue samples, were of very good quality. The fluorescent signals were well balanced across the nine STR loci or six loci comprised in the megaplexes surveyed and profiles showed no differences with those observed for the control blood of the respective donor patients. Continuous exposure to GenoFix at room temperature (up to one year and seven months) did not compromise the STR typing analysis of the fixed tissues. No adverse effects were noted on the STR typeability of tissues fixed with GenoFix and stored at -20 degrees C in a freezer for up to 3 1/2 years. STR profiles generated from the paraffin-embedded tissues fixed in GenoFix were of excellent quality. This preliminary study suggests that GenoFix can be used to store tissue samples at room temperature for up to one year and seven months or at -20 degrees C in a freezer for longer storage (up to 3 1/2 years). This new and odorless tissue fixative promotes tissue and DNA preservation in a very effective manner and as such may prove useful in criminal investigations or mass disaster identifications carried out in remote locations and in which a small or large number of tissue samples are collected for further analyses.

Biopsy↗