Search PubMed⌕ Search

Biomedical subjects

C J Weber

Publications and source records attributed to C J Weber.

At least 37 records · Page 2Linked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

Vasoactive intestinal polypeptide-, neurotensin-, substance P-, gastrin-releasing peptide-, calcitonin-, calcitonin gene related peptide-, and somatostatin-like immunoreactivities in human parathyroid glands.

We have found vasoactive intestinal polypeptide (VIP)-, neurotensin-, substance P-, gastrin-releasing peptide-, calcitonin-, calcitonin gene related peptide (CGRP-2)-, and somatostatin-like immunoreactivities in extracts of sporadic human parathyroid adenomas (n = 18). The content of CGRP-2, substance P, and somatostatin in adenomas correlated directly with that of parathyroid hormone. In addition, concentrations of VIP versus substance P and somatostatin versus CGRP-2 in adenomas were directly correlated. Neuropeptide content of parathyroid hyperplasias differed from that of adenomas. VIP was detected in only one of seven parathyroid hyperplasias, and neurotensin was undetectable (0/7), whereas substance P was present in six of seven cases and GRP in five of seven hyperplasias. In hyperplasias, content of substance P correlated directly with that of gastrin-releasing peptide. Peroxidase immunohistochemistry localized VIP-like immunoreactivity to 20% to 50% of both chief and oxyphilic cells and rare clear cells and capillary endothelium in 11 of 12 adenomas studied. Focal staining was present in glandular epithelium of the rim of adjacent normal parathyroid tissue and in two of three normal parathyroid glands removed with thyroid goiters. This staining was both cytoplasmic and apical membrane. By contrast, in adenomas, neurotensin- and substance P-like positivities were confined to scattered (5% to 10%) oxyphilic cells. Cytoplasmic positivity for parathyroid hormone, noted in 30% to 70% of cells in serial sections, confirmed that these tissues were indeed parathyroid glands.

Adenoma↗
PubMed1991

2-D echocardiography: emergent use in the evaluation of penetrating precordial trauma.

Diagnosis of cardiac injury in stable patients suffering penetrating precordial trauma has relied on observation, subxiphoid window, or exploratory thoracotomy. Previous reports have stressed the need for an alternative noninvasive diagnostic test. Although the use of echocardiography (ECHO) in this patient population has been suggested, to our knowledge no report thus far has presented extensive experience with this technique. We present our experience over 3 years with 36 patients in whom emergent ECHO was used as part of their initial work-up. Injuries included single stab wounds (17), multiple stab wounds (14), and gunshot wounds (5). Four patients (11%) had jugular venous distention, and 12 (33%) were tachycardic. None had a systolic blood pressure below 90 mm Hg. Four ECHOs (11%) were positive for pericardial effusion. No valvular abnormalities were detected. Three of the effusions were small and these patients were triaged to monitored beds and observed. All three effusions resolved on serial echocardiography. The fourth patient underwent an uneventful operative repair of a left ventricular laceration. Although the yield is low, emergent 2-D ECHO is a valuable tool in the triage of stable penetrating trauma patients when cardiac injury is suspected. Patients without effusion can be discharged or triaged to a ward bed. Small effusions can be observed in a monitored setting with serial examinations, while large effusions should be treated surgically. Echocardiography is less expensive than ICU admission and less invasive than either subxiphoid window or thoracotomy. There are no known complications associated with the procedure and it is recommended for emergent use when available.

Adult↗
PubMed1990

The role of CD4+ helper T cells in the destruction of microencapsulated islet xenografts in nod mice.

Islet transplants for large numbers of patients with diabetes will require xenografts. Microencapsulation is an appealing method for islet xenografting. However, graft function has been limited by a cellular reaction, particularly intense in spontaneously diabetic, NOD mice. The purpose of this study was to elucidate the mechanism of this reaction. Poly-1-lysine-alginate microcapsules containing 4000-12,000 dog or 1800-2000 rat islets were xenografted intraperitoneally into streptozotocin (SZN)-diabetic C57BL/6J and NOD mice, with or without recipient treatment with GK 1.5 (anti-CD4 monoclonal antibody) (20-30 microliters i.p. every 5 days, begun on day -7. Grafts were considered technically successful if random blood glucose (BG) was normalized (less than 150 mg/dl) within 36 hr. Graft failure was defined as BG greater than 250 mg/dl. Dog and rat islets in microcapsules normalized BG in both SZN and NOD mice within 24 hr routinely. Empty microcapsules and GK 1.5 treatments alone did not affect BG. NODs destroyed both microencapsulated dog and rat islets more rapidly than did SZN-diabetic mice (P less than .01). Graft biopsies showed an intense cellular reaction, composed of lymphocytes, macrophages and giant cells, and no viable islets. GK 1.5 treatment significantly prolonged both dog-to-NOD and rat-to-NOD grafts (P less than 0.01). Biopsies of long-term functioning grafts (on days 65-85) demonstrated viable islets and no cellular reaction around microcapsules; 1/4 rat and 1/8 dog islet xenografts continued to function indefinitely in NOD recipients, even after cessation of GK 1.5 therapy. Prediabetic NODs receiving encapsulated dog or rat islets mounted a moderate cellular reaction to grafts. Empty microcapsules excited no cellular reaction in diabetic or prediabetic NODs. We conclude that the NOD reaction to microencapsulated xenogeneic islets is helper T cell-dependent, and that the target of this reaction is not the microcapsule itself, but the donor cells within.

Animals↗
PubMed1990

Effects of tamoxifen and somatostatin analogue on growth of human medullary, follicular, and papillary thyroid carcinoma cell lines: tissue culture and nude mouse xenograft studies.

The knowledge that (1) the normal thyroid contains somatostatin, (2) polypeptide growth factors influence thyroid cell function, and (3) thyroid cells contain steroid hormone receptors prompted us to add somatostatin analogue No. 201-995 (SMS) (5 ng/ml) and/or tamoxifen citrate (TAM) (5 mumol/L) to 7-day monolayer cultures (50,000 cells/well) of three separate human thyroid carcinoma cell lines: DR081 (medullary), WR082 (follicular), and NPA'87 (papillary). Results, tabulated as cell numbers/well (X10(5) on day 7, revealed that TAM inhibited growth of medullary and follicular cells and that TAM plus SMS inhibited growth of papillary cells. In vivo studies of subcutaneous tumor cell xenografts in nude mice have documented that TAM (5 mg subcutaneous pellet) significantly inhibits the growth of medullary implants. Flow cytometric DNA studies of medullary cell cultures demonstrated a reduced G2 + M phase with TAM treatment. For papillary cell implants, TAM plus SMS (5 micrograms subcutaneously, twice daily) did not suppress tumor growth. All three cell lines were negative for estrogen receptor; addition of estradiol (5 ng/ml) to medullary cell cultures neither stimulated replication nor reversed the inhibitory effects of TAM in vitro. We conclude that (1) TAM slowed the growth of a cell line of human medullary carcinoma, both in vitro and in vivo; (2) this effect was not reversed by estradiol; (3) TAM plus SMS inhibited replication of a papillary carcinoma cell line in vitro, but not in vivo; and (4) TAM alone and TAM plus SMS inhibited replication of cultures of a human follicular thyroid carcinoma cell line. TAM and SMS may be useful in treatment of some human thyroid carcinomas.

Adenocarcinoma↗
PubMed1990

Microencapsulated dog and rat islet xenografts into streptozotocin-diabetic and NOD mice.

Microencapsulation is an appealing method for islet xenografting. However, graft failure has been related to a cellular reaction, particularly intense in spontaneously diabetic, NOD mice. The goal of this study was to characterize this reaction. Poly-l-lysine-alginate microcapsules containing dog or rat islets were xenografted intraperitoneally into streptozotocin (SZN)-diabetic C57BL/6J and spontaneously diabetic NOD mice, with or without recipient treatment with GK 1.5 (anti-CD4 monoclonal antibody). Both dog and rat islets in microcapsules normalized blood glucose (BG) routinely in both SZN and NOD mice within 24 hours. Empty microcapsules and GK 1.5 treatment did not affect BG. NODs destroyed both microencapsulated dog and rat islets more rapidly than did SZN-diabetic mice (P less than 0.01). Graft biopsies showed an intense cellular reaction and no viable islets. GK 1.5 treatment significantly prolonged both dog-to-NOD and rat-to-NOD grafts (P less than 0.01). Biopsies of long-term functioning grafts (on days #70-#95) demonstrated viable islets and no cellular reaction. In prediabetic NODs, encapsulated dog and rat islets elicited a moderate cellular reaction. Empty microcapsules excited no cellular reaction in either diabetic or prediabetic NODs.

Animals↗
PubMed1989

Gastrin-releasing peptide-, calcitonin gene-related peptide-, and calcitonin-like immunoreactivity in human breast cyst fluid and gastrin-releasing peptide-like immunoreactivity in human breast carcinoma cell lines.

To assess the role of growth factors in proliferative disorders of the breast, we assayed breast cyst fluid from 70 patients for calcitonin-related peptides. Cyst fluids (5.4 +/- 6.6 ml) (mean +/- SD) (n = 70) contained 10,499 +/- 8272 pg/ml of gastrin-releasing peptide (GRP)-like immunoreactivity in 66 of 70 samples. Calcitonin gene-related peptide (CGRP)-like immunoreactivity was found in 64 of 64 samples tested (3842 +/- 2048 pg/ml). Calcitonin-like immunoreactivity was detected in 47 of 69 samples (185 +/- 106 pg/ml). Significant correlations were found for GRP versus volume, CGRP, and calcitonin, for calcitonin versus volume and CGRP, and for CGRP versus volume. Extracts of two human breast carcinoma cell lines (MCF-7 and BT-20) contained measurable GRP-like immunoreactivity. We conclude that GRP-, CGRP-, and calcitonin-like immunoreactivities are present in human breast cyst fluid and that GRP-like immunoreactivity is present in two established human breast carcinoma cell lines. High concentrations of GRP-like immunoreactivity in both breast cyst fluid and breast carcinoma tissue, taken together with the known mitogenic and trophic activities of this peptide, support the hypothesis that GRP may be an important factor in human breast disease.

Biomarkers↗
PubMed1988

Measurement of 6-keto-PGF1 alpha and thromboxane B2 levels in critically ill surgical patients.

Systemic arterial and mixed venous plasma concentrations of 6-keto-PGF1 alpha and TxB2 were measured by radioimmunoassay in 63 critically ill patients with major trauma (n = 20) or sepsis (n = 43). Patients undergoing elective catheterization procedures served as controls (n = 10). Arterial and mixed venous 6-keto-PGF1 alpha and TxB2 levels were significantly elevated in patients with recent major trauma or active sepsis. The 6-keto-PGF1 alpha levels were found to be significantly elevated in the non-survivors and in patients with hepatic failure. The presence of severe pulmonary failure was not associated with increased levels of either 6-keto-PGF1 alpha or TxB2. Comparison of arterial and mixed plasma samples did not demonstrate increased pulmonary release of either compound. Increased eicosanoid production may account, in part, for the local vascular and humoral responses to tissue injury or infection.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Passage of somatostatin analogue across human and mouse skin.

Recent studies have documented beneficial effects of the somatostatin analogue, SMS 201-995 (hereafter referred to as SMS), when administered subcutaneously to patients with a variety of disorders. Since SMS is a small peptide, we tested the ability of two penetrant enhancers--dimethylsulfoxide and N-decylmethylsulfoxide (C10MS)--to promote transcutaneous passage of SMS. Samples of skin from human cadavers and hairless mice were tested in a static diffusion chamber. Application of SMS in conjunction with 1% C10MS resulted in rapid transdermal passage of SMS. These data were confirmed for hairless mouse skin in experiments with a modified diffusion chamber having continuous flow-through of receptor fluid in the subdermal reservoir. In this system, the cumulative amount of SMS that permeated hairless mouse skin was 20 micrograms/cm2/24 hours. Topical application of SMS with C10MS beneath a patch to mice confirmed in vitro data. Topical application of 10 micrograms of SMS resulted in plasma SMS levels of greater than 8,000 pg/ml within 2 hours. We conclude that SMS will cross both human and mouse skin, with a clinically significant flux, when administered topically with C10MS. The data support the feasibility of in vivo human trials of topical SMS therapy.

Administration, Cutaneous↗
PubMed1986

Prostaglandin E1 and survival in patients with the adult respiratory distress syndrome. A prospective trial.

A 7-day infusion of prostaglandin E1 (PGE1), an immunomodulator, was evaluated in a prospective, randomized, placebo-controlled, double-blinded trial in surgical patients with the adult respiratory distress syndrome (ARDS). The drug seemed to improve pulmonary function--only two PGE1 patients died with severe pulmonary failure compared with nine placebo patients (p = 0.01). Survival at 30 days after the end of the infusion--the predetermined end point of the study--was significantly better in the patients given PGE1 (p = 0.03), with 15 of 21 PGE1 patients (71%) alive at this time compared with seven of 20 placebo patients (35%). Improvement in overall survival in the PGE1 patients did not reach statistical significance (p = 0.08). Overall survival in patients initially free of severe organ failure, however, was significantly better in the PGE1 patients (p = 0.03). Of the six PGE1 patients free of severe organ failure at time of entry, all survived to leave the hospital; of the 10 placebo patients initially free of severe organ failure, four survived. The drug had no serious side effects and did not potentiate susceptibility to infection. PGE1 is a promising agent for the treatment of ARDS.

Adolescent↗
PubMed1985

Comparative evaluation of three identification systems for anaerobes.

The accuracy of two new 4-h identification systems for anaerobes, the AN-IDENT (Analytab Products, Plainview, N.Y.) and the RapID ANA (Innovative Diagnostic Systems, Inc., Atlanta, Ga.) was compared with that of the API 20A system (Analytab Products). A total of 132 clinical isolates were tested in each of the three systems. The overall accuracies at the genus and species level for the three systems were: API 20A, 68.9 and 56.8%, respectively; AN-IDENT, 90.2 and 73.5%; and RapID ANA, 93.9 and 81.8%. Improved identification of anaerobes with the AN-IDENT and the RapID ANA systems was observed for isolates of the genus Fusobacterium, Clostridium species other than Clostridium perfringens, non-spore-forming bacilli, and isolates of the genus Peptostreptococcus. Reproducibility studies demonstrated that the results of the individual test reactions in all three identification systems were reproducible when the interpretive guidelines of the manufacturer were followed precisely.

Bacteria, Anaerobic↗
PubMed1985

Presence of neuron-specific enolase and somatostatin in human parathyroid tissues.

The association of parathyroid abnormalities with apudomas prompted us to examine parathyroid tissues for the presence of neuron-specific enolase and somatostatin. Enolase was present in extracts of 29 out of 29 parathyroid specimens; tissue content was significantly higher in adenoma than in hyperplasia tissues (p less than 0.005). Somatostatin was present in 14 of 33 specimens. Immunoreactive somatostatin measured in tissue extracts' fluids coeluted on Sephacryl chromatography along with synthetic somatostatin-14 in studies of two parathyroid carcinoma specimens. Since neuron-specific enolase has been found only in neural and neuroendocrine cells, our results suggest that human parathyroid glands may contain neuroendocrine elements. The differential content of neuron-specific enolase in adenoma versus hyperplasia specimens may be diagnostically useful in selected cases. The significance of the presence of somatostatin in some but not all parathyroid tumors requires further investigation. Taken together with our prior findings of gastrin and pancreatic polypeptide in some human parathyroid glands, we postulate that human parathyroid tumors contain neural crest elements.

Adenoma↗
PubMed1983

Hypogastrinemia in streptozotocin diabetes with islet transplantation--reconstitution.

Gastrin is present in normal mammalian pancreatic islets, as well as in the antrum and duodenum. Serum gastrin levels are responsive to many physiologic and pharmacologic factors including hyperglycemia, somatostatin, and glucagon. To evaluate the effects of streptozotocin diabetes and islet transplantation on gastrin homeostasis, young, adult, male Lewis rats underwent streptozotocin diabetes alone (N = 14), diabetes plus intraperitoneal islet isografts (N = 22), or sham operation alone (N = 18). Streptozotocin reduced fasting gastrin immunoreactivity (107 pg/ml +/- 26 mean +/- SEM) compared to controls (256 pg/ml +/- 31) (P less than 0.001). Islet isotransplantation resulted in restoration of fasting gastrin immunoreactivity (230 pg/ml +/- 19) to levels significantly greater than diabetics (P less than 0.001) and comparable to control animals (P = NS). Normalization of serum gastrin levels occurred within one month of transplantation and persisted for up to 14 months. In addition, media from cultures of 4/7 dispersed neonatal rat pancreas cultures contained gastrin immunoreactivity. Streptozotocin diabetes produces hypogastrinemia; intraperitoneal islet isotransplantation normalizes fasting gastrin immunoreactivity. Rat islet culture medium contains gastrin-like immunoreactivity. Pancreatic islets would appear to produce or control a portion of circulating gastrin immunoreactivity.

Animals↗
PubMed1983

Detection of Clostridium difficile cytotoxin in HEp-2 and CHO cell lines.

The detection of Clostridium difficile cytotoxin was compared in two established cell lines; Chinese hamster ovary (CHO) and a human epithelial line, HEp-2. All specimens with positive toxin assays were detected with the CHO cell line, whereas only one-half of positive specimens were detected with the HEp-2 cells.

Animals↗