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Biomedical subjects

C J Weber

Publications and source records attributed to C J Weber.

At least 19 recordsLinked to original sources

Production and applications of biobased packaging materials for the food industry.

Materials based on renewable resources are being developed at an increasing rate. Today, the only biobased food-packaging materials used commercially on a major scale are based on cellulose. However, materials based on proteins, starch, polylactate and other renewable resources may be the food-packaging materials of tomorrow. The paper presents some of the different biobased materials and their potential as food-packaging materials.

Biodegradation, Environmental↗

Nuclear envelope organization in papillary thyroid carcinoma.

Papillary thyroid carcinomas (PTCs) have characteristic nuclear shape changes compared to follicular-type thyroid epithelium. We tested the hypothesis that the altered nuclear shape results from altered distribution or expression of the major structural proteins of the nuclear envelope. Lamin A, lamin B1, lamin C, lamin B receptor (LBR), lamina-associated polypeptide 2 (LAP2), emerin, and nuclear pores were examined. PTC's with typical nuclear features by H&E were compared to non-neoplastic thyroid and follicular neoplasms using confocal microscopy, and semi-quantitative immunoblotting. Lamin A/C, lamin B1, LAP2, emerin, and nuclear pores all extend throughout the grooves and intranuclear inclusions of PTC. Their distribution and fluorescent intensity is not predictably altered relative to nuclear envelope irregularities. By immunoblotting, the abundance (per cell) and electrophoretic mobilities of lamin A, lamin B1, lamin C, emerin, and LAP2 proteins do not distinguish PTC, normal thyroid, or follicular neoplasms. These results do not support previously published predictions that lamin A/C expression is related to a loss of proliferative activity. At least three LAP2 isoforms are identified in normal and neoplastic thyroid. LBR is sparse or undetectable in all the thyroid samples. The results suggest that the irregular nuclear shape of PTC is not determined by these nuclear envelope structural proteins per se. We review the structure of the nuclear envelope, the major factors that determine nuclear shape, and the possible functional consequences of its alteration in PTC.

Blotting, Western↗

The intracytoplasmic domain of the Env transmembrane protein is a locus for attenuation of simian immunodeficiency virus SIVmac in rhesus macaques.

The human and simian immunodeficiency virus (HIV-1 and SIVmac) transmembrane proteins contain unusually long intracytoplasmic domains (ICD-TM). These domains are suggested to play a role in envelope fusogenicity, interaction with the viral matrix protein during assembly, viral infectivity, binding of intracellular calmodulin, disruption of membranes, and induction of apoptosis. Here we describe a novel mutant virus, SIVmac-M4, containing multiple mutations in the coding region for the ICD-TM of pathogenic molecular clone SIVmac239. Parental SIVmac239-Nef+ produces high-level persistent viremia and simian AIDS in both juvenile and newborn rhesus macaques. The ICD-TM region of SIVmac-M4 contains three stop codons, a +1 frameshift, and mutation of three highly conserved, charged residues in the conserved C-terminal alpha-helix referred to as lentivirus lytic peptide 1 (LLP-1). Overlapping reading frames for tat, rev, and nef are not affected by these changes. In this study, four juvenile macaques received SIVmac-M4 by intravenous injection. Plasma viremia, as measured by branched-DNA (bDNA) assay, reached a peak at 2 weeks postinoculation but dropped to below detectable levels by 12 weeks. At over 1.5 years postinoculation, all four juvenile macaques remain healthy and asymptomatic. In a subsequent experiment, four neonatal rhesus macaques were given SIVmac-M4 intravenously. These animals exhibited high levels of viremia in the acute phase (2 weeks postinoculation) but are showing a relatively low viral load in the chronic phase of infection, with no clinical signs of disease for 1 year. These findings demonstrated that the intracytoplasmic domain of the transmembrane Env (Env-TM) is a locus for attenuation in rhesus macaques.

Animals↗

Evaluation of graft-host response for various tissue sources and animal models.

The efficacy of pancreatic islet transplants in correcting hyperglycemia and slowing the progression of complications in diabetics has been confirmed by many experimental and clinical studies. Unfortunately, the availability of human islets is extremely limited and, therefore, treatment of large numbers of human diabetic patients will almost certainly require either the use of islets harvested from animals (xenografts) or the use of insulin-secreting genetically modified cells of either human or animal origin. There is currently no effective regimen which will allow long-term survival of xenogeneic islets from widely unrelated donor-recipient combinations, such as pig-to-rodent, pig-to-dog, or pig-to-primate. There is considerable interest in the development of immunoisolation techniques for protection of donor islets. However, most materials used in immunoisolation devices are relatively bio-incompatible. Poly-L-lysine-alginate microcapsules are biocompatible and provide an optimal geometry for transmembrane diffusion of insulin and nutrients. Microcapsules allow long-term survival of xenogeneic islets in diabetic rodents or dogs with induced diabetes. However, mice and rats with spontaneous diabetes destroy encapsulated islet grafts within 2 to 3 weeks. Biopsies reveal large numbers of macrophages, immunoglobulins and limited numbers of helper and cytotoxic T-cells in the peri-microcapsule environment of the peritoneal cavity. Cytokines have been identified in peritoneal fluid from mice with islet grafts and may play a role in encapsulated islet destruction. Targeted immunomodulation by treatment of recipients with either anti-helper T-cell antibodies, or fusion proteins which block costimulatory interactions between antigen presenting cells and host T-cells have demonstrated synergy in significant prolongation of encapsulated islet xenograft survival in NOD mice with spontaneous diabetes. Technical improvements in microcapsule design also have contributed to prolonged graft survival. "Double-wall" microencapsulation provides a more durable microcapsule and islet pretreatment prior to encapsulation reduces the frequency of defective capsules with islets entrapped in the membrane. Long-term durability of encapsulated islet grafts remains a concern and further improvements in microcapsule design are a prerequisite to clinical trials.

Animals↗

Laparoscopic adrenalectomy: new gold standard.

Nearly 600 cases of laparoscopic adrenalectomy have been described in the world literature, documenting the safety and effectiveness of the procedure. Comparative studies have demonstrated the advantages of the laparoscopic approach when compared to traditional open approaches to adrenalectomy, documenting a more rapid and comfortable recovery, shorter hospitalization, and fewer complications. Several techniques of laparoscopic adrenalectomy have been described. We prefer the transabdominal approach in the lateral decubitus position. Herein we report our experience with 28 adrenalectomies using this approach. Indications for adrenalectomy have been hyperaldosteronism (9), hypercortisolism (4), pheochromocytoma (3), incidentaloma (6), metastasis (3), lymphoma (1), angiomyolipoma (1), other (1). Average tumor size was 3.3 cm (1. 4-8.3 cm). Average operative time was 152 minutes (110-210 minutes), with left adrenalectomy taking slightly longer to perform than on the right (156 vs. 145 minutes). There were no intraoperative complications and one conversion to open adrenalectomy for a large metastatic lung cancer found to be invading the liver. One patient experienced left rib pain from a cannula site immediately at the costal margin. There were no other complications. Average length of hospitalization was 2.3 days (1-6 days). With this and others' experience, laparoscopic adrenalectomy has become the gold standard for adrenalectomy. This manuscript reviews the literature on laparoscopic adrenalectomy and describes the transabdominal lateral approach.

Adrenal Gland Diseases↗

Retrospective analysis of sequential changes in serum intact parathyroid hormone levels during conventional parathyroid exploration.

BACKGROUND: The purpose of this study was to assess sequential changes in serum parathyroid hormone (PTH) levels during conventional parathyroidectomy. METHODS: Sera were collected before and 10 minutes after resection of each parathyroid tumor from 112 consecutive patients and assayed postoperatively within 48 hours for PTH. RESULTS: PTH reductions corroborated cures for 94 of 112 cases (84%), including 70 of 71 patients with solitary adenomas (SAs). However, there were 15 false positives (13%), in which PTH decreased more than 50% within 10 minutes of resection of 1 parathyroid tumor while additional parathyroid tumors remained in situ (1 of 71 SAs, 4 of 6 double adenomas, 7 of 15 primary hyperplasias, and 3 of 17 tertiary hyperplasias). There were 3 false negatives (3%), with PTH unchanged, even though postoperative PTH and calcium values confirmed cure (1 SA, 1 primary hyperplasia, and 1 tertiary hyperplasia). There were only 2 of 112 failed explorations (1.8%), which would not have been avoided by PTH monitoring because both subsequently were found to have mediastinal parathyroid adenomas. CONCLUSIONS: We conclude that intraoperative PTH changes corroborated outcome in SA but may under-estimate the extent of resection required in parathyroid hyperplasia.

Adenoma↗

Role of the SH3-ligand domain of simian immunodeficiency virus Nef in interaction with Nef-associated kinase and simian AIDS in rhesus macaques.

The nef gene of the human and simian immunodeficiency viruses (HIV and SIV) is dispensable for viral replication in T-cell lines; however, it is essential for high virus loads and progression to simian AIDS (SAIDS) in SIV-infected adult rhesus macaques. Nef proteins from HIV type 1 (HIV-1), HIV-2, and SIV contain a proline-Xaa-Xaa-proline (PxxP) motif. The region of Nef with this motif is similar to the Src homology region 3 (SH3) ligand domain found in many cell signaling proteins. In virus-infected lymphoid cells, Nef interacts with a cellular serine/threonine kinase, designated Nef-associated kinase (NAK). In this study, analysis of viral clones containing point mutations in the nef gene of the pathogenic clone SIVmac239 revealed that several strictly conserved residues in the PxxP region were essential for Nef-NAK interaction. The results of this analysis of Nef mutations in in vitro kinase assays indicated that the PxxP region in SIV Nef was strikingly similar to the consensus sequence for SH3 ligand domains possessing the minus orientation. To test the significance of the PxxP motif of Nef for viral pathogenesis, each proline was mutated to an alanine to produce the viral clone SIVmac239-P104A/P107A. This clone, expressing Nef that does not associate with NAK, was inoculated into seven juvenile rhesus macaques. In vitro kinase assays were performed on virus recovered from each animal; the ability of Nef to associate with NAK was restored in five of these animals as early as 8 weeks after infection. Analysis of nef genes from these viruses revealed patterns of genotypic reversion in the mutated PxxP motif. These revertant genotypes, which included a second-site suppressor mutation, restored the ability of Nef to interact with NAK. Additionally, the proportion of revertant viruses increased progressively during the course of infection in these animals, and two of these animals developed fatal SAIDS. Taken together, these results demonstrated that in vivo selection for the ability of SIV Nef to associate with NAK was correlated with the induction of SAIDS. Accordingly, these studies implicate a role for the conserved SH3 ligand domain for Nef function in virally induced immunodeficiency.

Animals↗

Parathyroid hormone content distinguishes true normal parathyroids from parathyroids of patients with primary hyperparathyroidism.

The purpose of this study was to clarify the pathophysiology of primary hyperparathyroidism by looking for differences between parathyroids from eucalcemic patients and patients with primary hyperparathyroidism (HPT) with respect to the following parameters: intracellular parathyroid content of parathyroid hormone (PTH) and parathyroid hormone messenger RNA (PTH mRNA); and serum PTH and calcium levels of patients and patient age. Coded samples of human parathyroid biopsies were assayed for PTH content with a C-terminal-specific radioimmunoassay. Total cellular RNA was extracted, and PTH mRNA was quantified by dot-blot analysis. These results were tabulated along with associated data on patient age, preoperative serum PTH, and preoperative calcium levels. The content of PTH was significantly higher in true normal (TN) parathyroids than in parathyroids from patients with hyperparathyroidism. PTH content of adenomas and hyperplasias were similar. PTH content of normal parathyroids biopsied from patients with parathyroid adenomas (NA) was statistically higher than that of adenomas but statistically lower than that of TN parathyroids. PTH mRNA and PTH content were correlated (p < 0.001) for TN parathyroid glands; however, it was not true for glands (grossly normal or otherwise) in patients with HPT. Patient groups were similar with regard to mean patient age and intracellular PTH mRNA levels. Hypercalcemic patients were similar with regard to preoperative serum calcium and PTH levels. NA parathyroids, adenomas, and hyperplasias are different from TN parathyroids with regard to their PTH content. PTH mRNA was similar across all groups. The relation between intracellular PTH mRNA and PTH was significantly absent in patients with HPT compared with TN glands. Furthermore, we have found that PTH content of normal parathyroid in patients with adenoma is similar to that of hyperplastic and adenoma tissues. These data suggest that the PTH content of parathyroid tissues may be of use in differentiating normal from abnormal parathyroids.

Adenoma↗

DNA index and ploidy distinguish normal human parathyroids from parathyroid adenomas and primary hyperplastic parathyroids.

BACKGROUND: The goal of this study was to identify factors that might aid in diagnosis and intraoperative management of hyperparathyroidism. METHODS: We analyzed biopsy specimens of 242 parathyroids from 159 patients by use of flow cytometry and image cytometry (ICM) for DNA index (DI), defined as the content of nuclear DNA compared with that expected for a DNA diploid standard, for proliferative index (PI), and for ploidy (diploid versus aneuploid or tetraploid). RESULTS: True normal and normal parathyroids from patients with solitary adenomas were uniformly diploid. Abnormal ploidy (aneuploidy or tetraploidy) was identified frequently in adenomas and occasionally in hyperplasias with the exception that multiple endocrine neoplasia (MEN) biopsy specimens were uniformly diploid. DI for adenomas was similar to that for hyperplasias, and DI of both was higher than for normal glands. ICM-DI correlated positively with flow cytometry-DI and patient age and inversely with serum parathyroid hormone. PI was relatively low in all groups but was higher for hyperplasias versus normal parathyroids from patients with solitary adenomas and MEN versus non-MEN. PI correlated inversely with patient age. CONCLUSIONS: DI by ICM differentiates normal from abnormal parathyroids. DI might influence extent of resection in two- and three-gland hyperplasia and selection of the most appropriate gland for autografting and cryopreservation in patients with four-gland hyperplasia.

Adenoma↗

Blood-to-tissue albumin transport in rats subjected to acute hemorrhage and resuscitation.

Hemorrhage induces a rapid redistribution of protein from extravascular spaces into the blood. We studied the effects of acute, nontraumatic hemorrhage on tracer-albumin clearances into individual tissues of rats to determine if reduced protein extravasation could account for intravascular protein gain. Three groups were studied: 1) HEM animals were anesthetized with pentobarbital sodium and bled to a mean arterial pressure of 50 mmHg for 90 min; 2) HEM-RS animals were treated identical to group 1 and then resuscitated with 5% bovine serum albumin (BSA) until baseline arterial pressures were regained; 3) SHAM animals served as time controls. Hemodynamic variables were measured periodically throughout hemorrhage and clearance periods, and plasma samples were collected prior to death for protein and hormone analysis. Plasma clearance of 131I-BSA into individual tissues was measured over the final 30 min of each protocol with a terminal injection of 125I-BSA used to correct for intravascular volume. Reduction of blood volume by 35% in HEM-treated animals resulted in a marked decrease in albumin transport relative to the SHAM group (p < or = .05) in the following tissues: skeletal muscle (-65%), skin (-49%), ileum (-75%), cecum (-66%), colon (-67%), heart (-67%), and lung (-71%). Significant changes were not observed in the remaining tissues sampled: pancreas, kidney, and cerebrum. Albumin clearances in the HEM-RS group were slightly but not significantly lower than SHAM animals except for skeletal muscle, where transport remained depressed following resuscitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Relationships of Na+ and K+ concentrations to GRP, CGRP, and calcitonin immunoreactivities and Na+,K(+)-ATPase (NKA) inhibitory activity in human breast cyst fluid.

BACKGROUND: Although the etiology of gross cystic disease of the breast is unknown, elevated cyst concentrations of potassium (K+) (> 60 mM/L) may be related to symptoms. The purpose of this study was to clarify the mechanism(s) of K+ accumulation in breast cysts. METHODS: We assayed cyst fluids for factors known to exert effects on K+ transport, namely, endogenous digitalis-like inhibitors of Na+,K(+)-ATPase (NKA) and the neuropeptides gastrin-releasing peptide (GRP), calcitonin (CT), and calcitonin gene-related peptide (CGRP). RESULTS: Cyst fluid K+ was directly correlated with cyst volume, cyst NKA inhibitory activity (in ouabain equivalents), and cyst concentrations of calcitonin, GRP, and CGRP. Cyst fluid Na+ was inversely correlated with cyst fluid K+, cyst NKA inhibitory activity, cyst volume, and cyst fluid concentrations of calcitonin, GRP, and CGRP. NKA inhibitory activity correlated directly with GRP and CGRP. Immunocytochemistry localized GRP to breast cyst lining cells and areas of ductal and lobular epithelial hyperplasia in biopsies of 15 of 15 cysts and in 5 of 5 breast carcinomas, but not in (0 of 5) normal breast biopsies. Specificity of GRP staining was demonstrated by total abolition of reactivity after adsorption with synthetic GRP, but not after adsorption with synthetic substance P, neurokinin A, or neurokinin B. CONCLUSIONS: We conclude that both the concentrations of endogenous digitalis-like factors and the neuropeptides calcitonin, GRP, and CGRP in human breast cyst fluids are related to the concentrations of K+ and Na+ in breast cysts and to cyst volume.

Adult↗

Persistent and recurrent sporadic primary hyperparathyroidism: histopathology, complications, and results of reoperation.

BACKGROUND: Our purpose was to analyze the causes of persistent and recurrent sporadic primary hyperparathyroidism (PD and RD). METHODS: The histopathology, complications, and results of reoperation were studied. Five hundred sixty-eight patients with primary hyperparathyroidism were operated on initially by one surgeon and underwent follow-up examination for 3.7 +/- 3.8 years. During the operation, all parathyroids were sought and confirmed by biopsy. Enlarged glands were resected, and subtotal parathyroidectomy was done for multiglandular disease (hyperplasia). RESULTS: The cure rate after the initial surgical procedure was 96.4%, PD = 2.8% (16 of 568). At reoperation (10 of 16), nine of 10 were cured (90%) (two adenomas, six hyperplasias, one lung carcinoma). RD was documented (at years 4, 4, 10, 15, 16) in five (0.9%) patients, one with parathyroid carcinoma and four with hyperplasia. Thirty-five patients with PD and two patients with RD were referred for reoperation: 17 with adenomas (eight mediastinal) and 18 with hyperplasias (one mediastinal gland). Preoperative calcium level was higher for PD (12.57 mg/dl) and RD (13.89 mg/dl) versus all cases (12.19 mg/dl) (p < 0.03 and p < 0.0005, respectively). After reoperation, normocalcemia was achieved in 47 (92.%) of 51 patients with PD or RD. Transient hypocalcemia occurred in 22% of patients (permanent, 2.0%) and transient hoarseness in 2.0% of patients (no permanent nerve damage). Permanent hypocalcemia and nerve damage after 568 initial operations were 0% and 0%, respectively. Two perioperative deaths occurred. CONCLUSIONS: We conclude that inadequate neck exploration or resection of hyperplastic tissue accounts for most cases of PD and RD. Optimal results necessitate intraoperative identification of all parathyroids whenever possible, with minimal morbidity.

Adult↗

Value of technetium 99m sestamibi iodine 123 imaging in reoperative parathyroid surgery.

BACKGROUND: The purpose of this study was to assess the contribution of technetium 99m sestamibi iodine 123 (T/S) imaging to preoperative and intraoperative management of patients with persistent hyperparathyroidism. METHODS: During a period of 10 months, all patients being prepared for reoperative parathyroid surgery (n = 10), two patients deemed significant operative risks (one patient with severe chronic obstructive pulmonary disease and one patient with severe cervical spine ankylosing spondylitis), and two patients who had undergone prior thyroid operation were studied with T/S imaging. Six patients undergoing reoperative surgery had undergone one, three had undergone two, and one had undergone three prior procedures. RESULTS: T/S imaging correctly localized 14 of 16 parathyroid tumors. By comparison, only 1 of 6 thallium technetium and 3 of 12 computed tomography (CT) scans (in seven patients) were positive. T/S imaging guided the reoperative surgical approach accurately in 12 of 14 patients, including one case of an undescended left lower gland at the level of the mandible and identification of a third gland on the left in another case. Sternal split was required to remove three lesions localized by T/S imaging, two beneath the aortic arch and one nestled in the aortopulmonary window in a patient who had undergone two prior procedures including a sternal split. In these three cases T/S imaging was particularly useful, because CT scans, thallium technetium scans, magnetic resonance imaging, and arteriography were not diagnostic. The outcome after operation was favorable in all 14 cases, with correction of hypercalcemia and no permanent laryngeal nerve injuries or hypocalcemia. CONCLUSIONS: We concluded that T/S imaging is more accurate than thallium technetium and CT scans in evaluation of patients with persistent hyperparathyroidism.

Adult↗

Secondary survey following blunt trauma: a new role for abdominal CT scan.

Computerized tomographic (CT) scanning for blunt abdominal trauma has focused on initial emergency department evaluation. At our institution, CT scanning is often used on a delayed basis for unexplained drops in hematocrit, investigation of bony injuries, or subtle abdominal findings. We reviewed 268 such scans. Over 32 months, 487 CT scans were done for 5258 blunt trauma admissions. Of these scans, 268 (55%) were done 8-72 hours after admission on patients under observation. Scanning indications were a falling hematocrit (67%), associated injuries (28%), and abdominal tenderness (5%). Fifty of the 268 scans (19%) were positive for intra-abdominal abnormalities. Pleural effusions were seen in 82 (31%). Sixteen abdominal explorations were done. There was no difference in the pre-scan hematocrit drop in patients with normal scans (6.6%), positive scans (6.8%), and those who were explored (6.4%). There was one false positive (0.4%) and two false negative scans (0.8%). Conclusions. (1) A significant number of occult injuries, some life threatening, are detected by delayed CT scans. (2) Hematocrit drop under observation is not a good predictor of occult intra-abdominal injury. (3) Delayed CT scanning for occult abdominal injury is cost effective.

Abdominal Injuries↗

Nuclear magnetic resonance as a measure of cerebral metabolism: effects of hypertonic saline resuscitation.

UNLABELLED: Fears of central nervous system dysfunction from acute hypernatremia and hyperosmolarity with hypertonic saline resuscitation are often cited. We used high-energy phosphate nuclear magnetic resonance to investigate resuscitation effects on cerebral metabolism. Rats were instrumented for hemodynamic monitoring and fluid infusion and a phosphorus surface coil placed on their skulls. After shimming, baseline spectra were obtained. Animals were then bled for one hour to a mean arterial pressure (MAP) of 45 mm Hg, followed by resuscitation for one hour to a MAP of 75 mm Hg with lactated Ringer's (LR, n = 17) or 7.5% hypertonic saline (HS, n = 25). Spectra were obtained again and analyzed for the ratio of high-energy phosphocreatine (PCr) to low-energy inorganic phosphate (Pi). Intracellular hydrogen ion concentration [H+] was calculated from the PCr/Pi shift. [table: see text] CONCLUSIONS: (1) Hypertonic saline results in a decreased intracellular pH compared with LR without associated changes in high-energy phosphate metabolism. (2) Decreases in pH may be the result of cell dehydration rather than metabolic dysfunction.

Animals↗

Relationships of parathyroid hormone, parathyroid secretory protein, parathyroid hormone messenger RNA, parathyroid secretory protein mRNA, and replication in human parathyroid adenoma and secondary hyperplasia tissues and cultures.

BACKGROUND: The purpose of this study was to clarify the relationships of extractable and secreted parathyroid hormone (PTH) and parathyroid secretory protein (PSP) in human parathyroid tumors to PTH messenger RNA (mRNA), PSP mRNA, and cell replication. METHODS AND RESULTS: In tissue cultures of seven adenomas and five secondary hyperplasias, we found a direct correlation for secreted PTH versus PSP for both adenomas and secondary hyperplasias. Secreted PTH:PSP was elevated for adenomas (11:1) compared to that of secondary hyperplasias (2:1), and adenomas secreted significantly more PTH and PSP than did secondary hyperplasias. In extracts of eight adenomas and six secondary hyperplasias, the ratio of PTH:PSP was unexpectedly low (2:1) and similar for both adenomas and secondary hyperplasias. The ratio of extractable PTH mRNA:PSP mRNA was extremely low for both adenomas (1:7) and for secondary hyperplasias (1:5). Flow cytometry indicated that percent replication was inversely correlated with PTH mRNA and PSP mRNA. CONCLUSIONS: Increased PTH secretion by adenomas cannot be attributed to increased biosynthetic capacity because it is less than expected. Hypersecretion of PTH by adenomas and coincident marked reductions in PTH mRNA suggest either a defect in cytoplasmic storage of PTH or impairment of normal posttranslational degradation of PTH. As parathyroid tumor cells increase replication, PTH mRNA is reduced. Possible explanations for this include decreased PTH gene transcription or decreased mRNA half-life.

Adenoma↗