Enhancing productivity and sustainability of ravine lands through horti-silviculture and soil moisture conservation: A pathway to land degradation neutrality.

Ravine lands are the worst type of land degradation affecting soil quality and biodiversity. Crop production in such lands is impossible without adopting proper conservation measures. In-situ moisture conservation techniques could play an instrumental role in restoring ravine lands by improving soil moisture. We hypothesized that restoring ravine land through a combination of tree planting, fruit crop cultivation, and in-situ moisture conservation practice would result in significant improvements in productivity, profitability, and soil fertility. An experiment was conducted involving the combination of Malabar Neem (Melia dubia) and Dragon fruit (Hylocereus undatus) in conjunction with in-situ soil moisture conservation measures specifically involving half-moon structures (HM). The experiment was conducted under randomized block design (RBD) comprising eight treatments. These treatments include sole Melia cultivation (MD 3m × 3m), sole cultivation of dragon fruit (DF 3m × 3m), silviculture system (MDF-3m × 3m), horti-silviculture system with larger spacing (MDF-4m × 4m), sole Melia cultivation with in-situ moisture conservation (MDH-3m × 3m), sole Dragon fruit cultivation with in-situ moisture conservation (DFH-3m × 3m), horti-silviculture system of Melia and Dragon fruit with in-situ moisture conservation (MDFH-3m × 3m), and horti-silviculture system with larger spacing and in-situ moisture conservation (MDFH-4m × 4m). Each treatment was replicated thrice to evaluate their impact on productivity, profitability, soil fertility, and carbon sequestration for 8 years (2016-2023). The results revealed that the horti-silviculture system (MDFH-3 × 3 m) exhibited the highest total tree biomass and total carbon sequestration with an increase of 183.2% and 82.8% respectively, compared to sole Melia cultivation without HM and sole Melia with HM. Furthermore, sole Melia with HM augmented soil nutrients (N, P, K, and SOC) by 74.4%, 66.4%, 35.2%, and 78.3%, respectively, compared to control (no planting), with performance at par with MDFH-3 × 3 m. Similarly, sole Melia with HM enhanced SOC stock and SOC sequestration rate by 79.2% and 248% over control. However, it was found at par with MDFH-3 × 3 m. The horti-silviculture system (MDFH-3 × 3 m) consistently produced the highest fruit yield throughout the years surpassing other treatments. This treatment increased the average dragon fruit yield by 115.3% compared to sole dragon fruit without HM. Hence, the adoption of the horti-silviculture system (MDFH-3 × 3 m) could be a promising strategy for achieving enhanced environmental and economic benefits in ravine lands. Therefore, dragon fruit based horti-silviculture system (MDFH-3 × 3 m) could be recommended for restoration of ravine lands, improving land productivity, and mitigating impact of soil erosion particularly in Western India or similar agro-climatic regions of the world.

Assessing the diagnostic accuracy and interobserver agreement of MRI perfusion in differentiating disease progression and pseudoprogression following treatment for glioblastoma in a tertiary UK centre.

AIM: To assess the local diagnostic accuracy and interobserver agreement of dynamic susceptibility contrast-enhanced magnetic resonance perfusion (DSC MRP) reporting in differentiating between disease progression and pseudoprogression (PP) at a tertiary UK centre. MATERIALS AND METHODS: This retrospective study included adults with histology-proven glioblastoma who underwent an index DSC MRP examination following treatment. Each index examination was evaluated by three reporters independently, including qualitative assessment and measurement of mean regional cerebral blood volume (rCBVmean) ratios. Consensus opinion was used as the reference standard and considered clinical, radiological and histological follow-up information. Examination reports were compared to each other and to the consensus opinion. RESULTS: Thirty-two cases were included (19 progression, 13 pseudoprogression). Interobserver agreement was fair for qualitative opinion (κ=0.58, 95% confidence interval [CI] 0.40-0.76) and good for rCBVmean ratio measurement (intraclass correlation coefficient [ICC, two-way random effects model] 0.63, 95% CI=0.43-0.78). Qualitative opinion showed diagnostic accuracies of 77.1% (95% CI=67.4-85.1) for progression and 75% (95% CI=65.1-83.3) for pseudoprogression. rCBVmean ratios were higher for progression (6.85 ± 3.98) than pseudoprogression (3.71 ± 3.40); a 3.0 threshold value maximised the sum of sensitivity (91.1%) and specificity (69.7%) on receiver operating characteristic analysis. CONCLUSIONS: DSC MRP and rCBVmean ratio measurement aid differentiation between progression and pseudoprogression following treatment for glioblastoma. Measurement of the rCBVmean ratio shows good interobserver agreement and can change opinion and improve confidence in DSC MRP reporting. Individual centres should validate their own threshold rCBVmean ratio values to optimise diagnostic accuracy.

Agroforestry for controlling soil erosion and enhancing system productivity in ravine lands of Western India under climate change scenario.

Soil erosion in semi-arid climate leading to the development of ravine lands is the most severe form of land degradation. Ravine lands are formed when soil is not fully covered by the vegetation throughout the year and sporadic vegetation is not able to bind the soil particles from being washed away by rainfall. Throughout the globe, ravine lands have severe limitations for their rehabilitation and sustainable utilization as a consequence of its unique topographical features. Climatic and edaphic stresses make crop production extremely challenging in these lands. Practicing sole cropping promotes erosion, produces low crop yield, utilizes high energy, and emits greenhouse gasses (GHGs). Tree cultivation either sole or in combination with crops (agroforestry) has a strong potential to control erosion, produce sustainable economic yield, reduce energy consumption, and sequester greater amount of atmospheric carbon dioxide in biomass and soil carbon pools besides providing various ecosystem services. Therefore, practicing agroforestry could be a promising approach to obtain the greater environmental and economic benefits in the ravine lands. The present study was conducted on three systems, i.e., sole crop cultivation (cowpea + castor), agroforestry (sapota + cowpea + castor), and sole sapota plantation, to evaluate their impact on soil erosion, runoff, system productivity, profitability, energetics, and carbon sequestration during the 4-year period (2017-2020). The results revealed that agroforestry reduced the total soil loss and runoff by 37.7% and 19.1%, respectively, compared to the sole crop cultivation. Likewise, the highest system productivity as cowpea equivalent yield (CEY) was obtained under agroforestry system that increased the CEY by 162% and 81.9%, compared to sole crop and sole tree plantation, respectively. The climate change mitigation potential in terms of net carbon balance was observed highest in sole tree plantation (8.4 t/ha) followed by agroforestry system (5.9 t/ha) and lowest in sole cropping system (-2.8 t/ha). Therefore, an agroforestry system could be recommended for controlling soil erosion, improving system productivity and profitability, and reducing energy consumption as well as mitigating climate change in ravine lands.

The PNPLA3 I148M variant is associated with transaminase elevations in type 2 diabetes patients treated with basal insulin peglispro.

Basal insulin peglispro (BIL) is a novel insulin with hepato-preferential action. In phase 3 trials, BIL showed significantly improved glycemic control but higher levels of transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), triglycerides (TGs) and liver fat content (LFC) compared with insulin glargine (GL). As variants in PNPLA3 (I148M) and TM6SF2 (E167K) are associated with nonalcoholic fatty liver disease, we assessed these variants in type 2 diabetes (T2D) patients randomized to receive BIL (n=1822) or GL (n=1270) in three phase 3 trials. Magnetic resonance imaging assessments of LFC were conducted in a subset of patients (n=296). Analyses showed α-corrected significant increases in change from baseline in AST (P=0.0004) and nominal increases in ALT (P=0.019), and LFC (P=0.035) for PNPLA3 (148M/M) genotypes in the BIL arm at 26 weeks but no significant associations in GL. PNPLA3 (148M/M) was also associated with increases in total cholesterol (P=0.014) and low-density lipoprotein cholesterol (P=0.005) but not with hemoglobin A1c or TG. T2D patients with the PNPLA3 (148M/M) genotype treated with BIL may be more susceptible to increased liver fat deposition. The current data provide further insights into the biological role of PNPLA3 in lipid metabolism.

Trainee radiologist reports as a source of confirmation bias in radiology.

AIM: To assess and quantify the relationship between trainee reporting and radiology errors. MATERIALS AND METHODS: A retrospective analysis of the 100 most recent cases reviewed by a discrepancy forum in a tertiary neuroradiology service was performed. Data on the time of the scan and the presence of a trainee report were collected, with comparison being made between the cohort of erroneous reports and the overall service. RESULTS: Although out-of-hours imaging only constituted 18% of the overall service, 36% of erroneous reports originated from scans performed out-of-hours. Eighteen percent of scans were first reported by a trainee and then checked by a consultant, with the remaining 82% being solely reported by the consultant. Despite this, 52% of errors were from consultant-checked trainee reports. CONCLUSION: Although out-of-hours imaging has long been associated with error, this study identifies consultant checking of trainee reports as another error-associated reporting context. This is likely to relate to confirmation bias, in which the pre-existing trainee report may result in inattentional blindness on the part of the checking consultant. Awareness of this phenomenon is important for the reduction of error in this specific and widely underestimated reporting context.

Monitoring hospital wastewaters for their probable genotoxicity and mutagenicity.

Cancer is a leading cause of death worldwide. Excluding the genetic factors, environmental factors, mainly the pollutants, have been implicated in the causation of the majority of cancers. Wastewater originated from health-care sectors such as hospitals may carry vast amounts of carcinogenic and genotoxic chemicals to surface waters or any other source of drinking water, if discharged untreated. Humans get exposed to such contaminants through a variety of ways including drinking water. The aim of the present study was, thus, to monitor the genotoxic and mutagenic potential of wastewaters from three big hospitals located in Jaipur (Rajasthan), India. One of them was operating an effluent treatment plant (ETP) for treatment of its wastewater and therefore both the untreated and treated effluents from this hospital were studied for their genotoxicity. Two short-term bacterial bioassays namely the Salmonella fluctuation assay and the SOS chromotest were used for the purpose. Results of fluctuation assay revealed the highly genotoxic nature of all untreated effluent samples with mutagenicity ratios (MR) up to 23.13 ± 0.18 and 42.25 ± 0.35 as measured with Salmonella typhimurium strains TA98 and TA100, respectively. As determined with the chromotest, all untreated effluents produced significant induction factors (IF) ranging from 3.29 ± 1.11 to 13.35 ± 3.58 at higher concentrations. In contrast, treated effluent samples were found to be slightly genotoxic in fluctuation test only with an MR = 3.75 ± 0.35 for TA100 at 10 % concentration. Overall, the results indicated that proper treatment of hospital wastewaters may render the effluents safe for disposal contrary to the untreated ones, possessing high genotoxic potential.

Comparative oxidative stress, metallothionein induction and organ toxicity following chronic exposure to arsenic, lead and mercury in rats.

Globally, arsenic, mercury and lead constitutes as the three most hazardous environmental toxicants perturbing imbalance in pro­oxidant and antioxidant homeostasis. Individual toxicity of these environmental toxicants is well known but there is lack of comparative data on variables indicative of oxidative stress. We thus investigated the effects of chronic exposure to sodium arsenite, mercuric chloride and lead acetate on blood and tissue oxidative stress, metal concentration and metallothionein (MT) contents. Male rats were exposed to sodium arsenite, mercuric chloride and lead acetate (0.05 mg/kg each, orally, once daily) for 6 months. Arsenic, mercury and lead exposure led to a significant inhibition of blood δ­aminolevulinic acid dehydratase (ALAD) activity and glutathione level supported by increased thiobarbituric acid reactive substance (TBARS). The level of inhibition was more pronounced in case of lead followed by mercury and arsenic. These metals/ metalloid significantly increased reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS) and glutathione peroxidase (GPx) activity accompanied by a decreased superoxide dismutase (SOD), catalase and reduced and oxidized glutathione (GSH and GSSG) levels in blood and tissues. Mercury alone produced a significant induction of hepatic and renal MT concentrations. Serum transaminases, lactate dehydrogenase and alkaline phosphatase activities increased significantly on exposure to arsenic and mercury exposure suggesting liver injury which was less pronounced in case of lead exposure. These biochemical alterations were supported by increased arsenic, mercury and lead concentrations in blood and soft tissues. The present study suggests that exposure to sodium arsenite and mercuric chloride lead to more pronounced oxidative stress and hepatotoxicity while lead acetate caused significant alterations in haem synthesis pathway compared to two other thiol binding metal/metalloid.

Providing monovalent oral polio vaccine type 1 to newborns: findings from a pilot birth-dose project in Moradabad district, India.

PROBLEM: Poliovirus transmission remained a public health challenge in western Uttar Pradesh, India in late 2005 and early 2006. In 2006, the India Expert Advisory Group for Polio Eradication concluded that, given the peak incidence of polio among children 6 to 12 months of age, a targeted birth dose of oral polio vaccine may be necessary to interrupt intense poliovirus transmission in high risk areas. APPROACH: The Government of Uttar Pradesh, the National Polio Surveillance Project and the United Nations Children's Fund (UNICEF) implemented a pilot birth-dose project aimed at identifying and vaccinating all newborns with a dose of oral polio vaccine within 72 hours of birth in an effort to evaluate operational feasibility and potential impact on population immunity. LOCAL SETTING: The project was piloted in Moradabad district: zone 7 in Moradabad City (urban setting), Kunderki block (rural setting) and in select birthing hospitals. RELEVANT CHANGES: Between July 2006 and February 2007, 9740 newborns were identified, of which 6369 (65%) were vaccinated by project personnel within 72 hours of birth. Project coverage (for total newborns vaccinated) ranged from 39% (in zone 7) to 76% (in Kunderki block) of the estimated number of newborns vaccinated during previous supplemental immunization activities. LESSONS LEARNED: Birth-dose coverage among newborns was lower than expected. Expansion costs were estimated to be high, with marginal impact. The project, however, provided opportunities to strengthen newborn tracking systems which have increased the number of newborns and young infants vaccinated during supplemental immunization activities and enrolled in routine programmes.

Genotoxicity evaluation of hospital wastewaters.

In hospitals a large variety of substances are in use for medical purposes such as diagnostics and research. After application, diagnostic agents, disinfectants and excreted non-metabolized pharmaceuticals by patients reach the wastewater. Indeed, some of the substances found in wastewaters are genotoxic and are suspected to be a possible cause of the cancers observed in the last decades. Genotoxicity tests are an excellent means to study the toxicity and the risk associated with these releases. This paper points out the areas of concern for hospital wastewater disposal and reports the findings of genotoxicity tests for hospital effluents from 3 major hospitals in Delhi, namely All India Institute of Medical Sciences, Apollo and Escorts. Mutagenicity of hospital wastewaters from effluent treatment plants (before and after treatment) was studied. The results of this study show that the genotoxicity of hospital wastewaters is highly reduced after the treatment process. This study calls for establishment of advanced and effective effluent treatment plants in the hospitals, which are merely dumping the wastewaters in the municipal sewerage system. The results of this study call for further detailed study in this area.

Brain pseudotumour secondary to Behçet's disease.

Neuro-Behçet's disease (NBD) is a serious manifestation of Behçet's disease (BD) and can affect either the central or peripheral nervous systems, or both. It occurs in 10-50% of patients with BD. We report on a patient with an unusual intraparenchymal lesion, initially thought to be a brain tumour. Histological examination revealed vasculitis consistent with BD. Clinicians should include NBD as a differential diagnosis when considering an isolated inflammatory intracranial lesion.

Is the KUB radiograph redundant for investigating acute ureteric colic in the non-contrast enhanced computed tomography era?

AIM: To establish whether non-contrast enhanced computed tomography (NCCT) renders the kidneys-ureters-bladder (KUB) radiograph redundant as the initial imaging investigation for suspected acute ureteric colic. MATERIALS AND METHODS: The imaging investigations for 120 patients consecutively admitted to an emergency department-led clinical decisions unit (CDU) with suspected acute ureteric colic were retrospectively reviewed. A multidisciplinary meeting reviewed the findings and recommended that KUB radiographs should not be routinely performed prior to NCCT. Prospective assessment of 116 consecutive patients admitted over a comparable period was then undertaken. RESULTS: In the retrospective group, 61 (50.8%) patients had calculi to account for symptoms (positive NCCT) and 59 (49.2%) patients did not have stone disease (negative NCCT). Ninety (75%) patients had a KUB radiograph prior to NCCT. However, in 46 (38% of total) of these patients the NCCT was negative for stones, and therefore, they had been subjected to an unnecessary radiographic examination. These results prompted a change in practice. In the subsequent and prospectively studied group, preliminary KUB radiographs were performed in only 6% of the patients, with no significant change in the positive NCCT rate (50.8 versus 51.7%) or the total number of examinations performed (120 versus 116). CONCLUSION: NCCT should be the initial imaging examination for acute ureteric colic. Up to 50% of patients with clinical suspicion do not have stone disease, and therefore, preliminary KUB radiographs with attendant radiation and cost implications are unjustified. Preliminary KUB radiographs can be omitted from the imaging pathway with no resultant indication creep or increase in demand for NCCT examinations.

Application of commercial glasses for high dose measurement using the thermoluminescent technique.

Commercial glasses under this study showed linear thermoluminescence (TL) response in gamma dose range 100 Gy to 10 kGy, glow peaks between 175 and 200 degrees C, fading under dark and room light 2.86-7.36% and 10.42-20.82%, respectively, in 24h and 34.86-70.80% under sunlight in 5h after exposure. The TL glass dosimetric results have been found to be reproducible within +/- 6.0%. Glasses have been observed as thermally unstable and its TL sensitivity reduces after annealing. The TL response of the glasses has been found to reduce by 7.40-51.49% after first annealing of the samples at 400 degrees C for 15 min. The trace element study suggests that presence of impurities has no role in TL sensitivity of glasses rather imperfections and dislocations in the lattice are the major contributor in the formation of TL centers. Commercial glasses can serve as good TL material for gamma irradiator and gamma chamber dosimetry. The various radiation parameters for glass TL dosimetry have been studied in detail and presented.

Accidental gamma dose measurement using commercial glasses.

Commercial glasses have been investigated for their application in accidental gamma dose measurement using Thermoluminescent (TL) techniques. Some of the glasses have been found to be sensitive enough that they can be used as TL dating material in radiological accident situation for gamma dosimetry with lower detection limit 1 Gy (the dose significant for the onset of deterministic biological effects). The glasses behave linearly in the dose range 1-25 Gy with measurement uncertainty +/- 10%. The errors in accidental dose measurements using TL technique are estimated to be within +/- 25%. These glasses have shown TL fading in the range of 10-20% in 24 h after irradiation under room conditions; thereafter the fading becomes slower and reaches upto 50% in 15 d. TL fading of gamma-irradiated glasses follows exponential decay pattern, therefore dosimetry even after years is possible. These types of glasses can also be used as lethal dose indicator (3-4 Gy) using TL techniques, which can give valuable inputs to the medical professional for better management of radiation victims. The glasses are easy to use and do not require lengthy sample preparation before reading as in case of other building materials. TL measurement on glasses may give immediate estimation of the doses, which can help in medical triage of the radiation-exposed public.

Assessment of teratogenecity and embryotoxicity of sludge from textile industries at Pali (India) in Swiss albino mice exposed during organogenetic period.

The present investigation was carried out to assess the teratological effects of in-utero exposure of sludge leachate from textile and dyeing industries located in Pali, Rajasthan. Sludge was collected at the combined effluent treatment plant (CETP). Two groups of 10 pregnant Swiss albino mice each, were given sludge leachate of 1/10 and 1/100 dilutions with water ad libitum from 6th day to 15th day of gestation covering the critical period of organogenesis. Cesarean sections were performed on day 18 of gestation and all foetuses were examined for reproductive and teratological tests. Sludge induced maternal toxicity was evidenced by significant increase in leachate consumption, reduction in body weight gain and reduction in fur of the body. Developmental toxicity was evidenced by a significant decrease in foetal weight per litter increase in the number of resorptions and an increase in total number of foetuses showing bone retardation and skeletal variations (specially of skull, sternebrae and vertebrae). The leachate of the sludge that is being dumped in the open areas of the town Pall seems to elicit teratogenic as well as embryotoxic potential as indicated by the findings of the present investigation.

Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats.

Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a "calcilytic") of the parathyroid cell Ca(2+) receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17beta-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca(2+) receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis.

Anti-tumor effects of the bacterium Caulobacter crescentus in murine tumor models.

Caulobacter crescentus is a gram negative, non-pathogenic bacterium, common in aquatic and soil environments. One feature of note is a protein surface layer (S-layer) composed of a single protein, organized as a self-assembled crystalline array that coats the bacterium. In the course of efforts to express cancer-associated peptides as genetic insertions into the S-layer, we noted a tumor suppressive effect of the unmodified bacterium. C. crescentus was examined for anti-tumor activity against three transplantable tumor mouse models: Lewis lung carcinoma cells transfected with the MUC1 gene in C57BL/6, murine mammary carcinoma (EMT-6) in BALB/c (both in prophylactic and therapeutic mode) and murine leukemia cells (L1210) in DBA2. Mice were immunized three times i.p. with C. crescentus (2 x 10(7) cells/mouse). In prophylactic mode, the mice were challenged with tumor cells two weeks after the last immunization. Immunization with live C. crescentus resulted in anti-tumor activity in all three transplantable tumor models, as measured by prolonged survival, reduced tumor mass or reduced number of lung nodules, compared to saline control groups. In the Lewis lung and the EMT-6 mammary carcinoma murine models the number of lung nodules as well as the tumor weight was lower in mice treated with C. crescentus, compared to the control group; for EMT-6, this was observed in prophylactic and therapeutic modes. In the murine leukemia and Lewis lung carcinoma models prolonged survival was observed in the groups of mice immunized with Caulobacters. In most cases the live C. crescentus cells were markedly more efficacious than heat killed or formalin fixed cells, despite the fact that they do not grow or persist in mice. The results suggest that C. crescentus may be a safe, bacterial immunomodulator for the treatment of tumors.

In vivo modulation of hematopoiesis by a novel hematoregulatory peptide.

The hematoregulatory peptide dimer, HP5B, enhances myelopoiesis by stimulating stromal cell cytokine production. However, the disulfide bridge of this peptide is susceptible to reduction, leading to the formation of monomeric pentapeptide, HP5, a direct-acting inhibitor of myelopoiesis. We have replaced the disulfide (S-S) bond of HP5B dimer with an isosteric ethylene (CH2-CH2) group, creating a new, nonreducible, metabolically more stable peptide (SK&F 107647). This novel peptide was tested in vitro and in vivo for hematopoietic effects. In vitro, SK&F 107647 has no direct colony-stimulating activity (CSA). Stimulation of murine stromal cells with SK&F 107647 results in production and release of CSA at concentrations as low as 0.01 ng/mL, at least 10-fold lower than observed with HP5B dimer. Injection of SK&F 107647 in normal mice results in a two- to six-fold increase in serum CSA, which becomes maximal at 6 hours postinjection. Administration of peptide daily over 4 days (q.d. x 4) by both parenteral and oral routes results in significant increases in absolute numbers of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, as well as stimulating their cell cycle rates. A doubling in day 8 CFU-S was also observed in SK&F 107647-treated mice. Continuous subcutaneous (s.c.) infusion of SK&F 107647 in femorally cannulated rats demonstrated modest but significant elevation of peripheral blood neutrophil and monocyte counts within 7 days. SK&F 107647 represents a novel synthetic hematoregulatory peptide that shares biological and/or modulatory activities with natural hematopoietic cytokines.

Identification and characterization of calcitonin gene-related peptide receptors in porcine renal medullary membranes.

Membranes prepared from the medullary region of the porcine kidney displayed high affinity, high density (Kd, 0.12 nM; binding capacity, 127 fmol/mg protein) receptors for calcitonin gene-related peptide (CGRP). Human CGRP (hCGRP), rat CGRP (rCGRP), and the hCGRP analog [hCGRP-(8-37)] competed for the binding of [125I]hCGRP, whereas salmon calcitonin (sCT) and CGRP-(22-37) were very weak in displacing [125I]hCGRP binding. In accordance with these binding data, CGRP stimulated adenylate cyclase activity in these membrane preparations in a concentration-dependent manner, with an EC50 similar to that of the Kd for binding. In the same preparations, sCT was ineffective in stimulating adenylate cyclase activity, suggesting that porcine kidney medullary membranes possess receptors specific for CGRP. Further hCGRP-(8-37), a CGRP antagonist, inhibited CGRP-stimulated adenylate cyclase activity in a competitive manner. Covalent cross-linking of [125I]hCGRP to these membranes resulted in the specific labeling of one major band at approximately 30,000 mol wt and two minor bands at about 58,000 and 78,000 mol wt. The presence of CGRP receptors and their coupling to adenylate cyclase suggest a role for CGRP in kidney function, such as local regulation of the microcirculation, electrolyte transport, or water homeostasis in the porcine kidney.

Structure-activity relationships of novel hematoregulatory peptides.

Hematopoiesis is a lifelong cell renewal process regulated by a family of lineage specific hematopoietic growth factors. Several hematopoietic growth factors such as G-CSF, GM-CSF, and M-CSF have been clinically evaluated for enhancement of host defense in normal and immunocompromised patients and for the treatment of infectious diseases. This paper reports the structure-activity relationships of low molecular weight hematoregulatory peptides based on a nonapeptide (1, SK&F 107647). Like the macromolecular growth factors, these peptides modulate host defense. A molecular target for this class of compounds has not yet been identified. However, the structure-activity relationships established by this study implicate a very specific molecular recognition event that is pivotal for the biological activities of 1 and its analogues.

Antiserum to a novel peptide sequence reacts selectively with epithelial subpopulations.

A synthetic peptide corresponding to a novel protein sequence isolated from bovine kidney was used to immunize rabbits. When applied to Western blots of bovine kidney extracts, antiserum to this peptide recognizes proteins with molecular weights of 23 and 18 KD. Immunohistochemical examination of a variety of bovine and rat tissues with this antiserum revealed a unique distribution of immunoreactivity with the intermediate layers of a variety of stratified epithelia, in addition to renal glomeruli. The pattern of reactivity differed from previously described epithelial markers such as cytokeratins. These results indicate that this antiserum may be useful as a tool for the identification of cells of the intermediate layer of stratified epithelia and, as such, may aid in the study of this differentiating/proliferating tissue compartment.