[Pay attention to the clinical application of radiofrequency ablation in the treatment of neuropathic pain].

Neuropathic pain is the pain triggered or caused by primary damage and dysfunction of the nervous system. Its pathogenesis is complex, involving changes in ion channel function, abnormal action potential generation and expansion, and central and peripheral sensitization. Therefore, it has always been the most intractable problem in clinical pain diagnosis and treatment, and there are many kinds of treatment methods. In addition to various oral drugs, nerve block, pulsed radiofrequency, radiofrequency ablation, central nerve electrical stimulation, peripheral nerve electrical stimulation, intra-thecal infusion system, craniotomy nerve decompression or carding, the dorsal root entry zone disfigurement, etc. various methods have mixed efficacy. So far, radiofrequency ablation of peripheral nerves is still the most simple and effective means for the treatment of neuropathic pain. In this paper, the definition, clinical manifestations, pathological mechanism and the treatment methods of radiofrequency ablation of neuropathic pain were expounded, in order to provide reference for related clinicians in radiofrequency ablation.

[Efficacy of CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves in the treatment of Meige syndrome].

Objective: To evaluate the efficacy of CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves in the treatment of Meige syndrome. Methods: The Clinical data of 56 patients with Meige syndrome in the Department of Pain Medicine, Affiliated Hospital of Jiaxing University from June 2019 to January 2023 were retrospectively analyzed [19 males and 37 females, aged 42-76 (58.6±8.3) years], including 51 cases of blepharospasm, 3 cases of oromandibular dystonia and 2 cases of blepharospasm concomitant with oromandibular dystonia. CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves was performed on different types of Meige syndrome. And the efficacy and complications of the technique were observed. Results: Fifty-one patients with blepharospasm Meige syndrome underwent CT-guided radiofrequency of facial nerve through bilateral stylomastoid foramen punctures, the symptoms of blepharospasm disappeared completely, leaving bilateral mild and moderate facial paralysis symptoms. Three patients with oral-mandibular dystonia underwent CT-guided radiofrequency therapy by bilateral foramen ovale puncture of mandibular branches of trigeminal nerve, masticatory muscle spasm disappeared, the patients had no difficulty opening the mouth, and the skin numbness in bilateral mandibular nerve innervation area was left. Two cases of Meige syndrome with blepharospasm concomitant with oromandibular dystonia were treated by radiofrequency of facial nerve and mandibular branch of trigeminal nerve, and all symptoms disappeared. The patients were followed up for 1-44 months after the operation, and the symptoms of mild and moderate facial paralysis disappeared at (3.2±0.8) months after the operation, but the numbness did not disappear. Three patients with blepharospasm recurred at the 14, 18 and 22 months after the operation, respectively, while the rest cases did not recur. Conclusions: According to different types of Meige syndrome, CT-guided partial radiofrequency ablation of responsible cranial nerves can effectively treat the corresponding type of Meige syndrome. The complications are only mild and moderate facial paralysis which can be recovered, and/or skin numbness in the mandibular region.

[Comparison of criteria for metabolically healthy overweight/obesity in Shanghai Changfeng study].

Objective: To establish a more suitable and practicable criterion of metabolically healthy overweight/obesity (MHO/O) in Chinese, a comparison study on different criteria of MHO/O was conducted in subjects aged over 45-year-old in Shanghai Changfeng Community. Method: A total of 3 301 overweight/obese subjects over 45 years old (men 1 521, women 1 789) in Shanghai Changfeng Community was included in the study. According to the inclusion or exclusion of waist circumference (WC), homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.5, and numbers of abnormal metabolic components, the MHO/O criteria were divided into 7 types: Adult Treatment Panel Ⅲ (ATP-Ⅲ) (with WC)<1 component, ATP-Ⅲ (with WC)<2 components, ATP-Ⅲ (with WC)<3 components, ATP-Ⅲ (without WC)<1 component, ATP-Ⅲ (without WC)<2 components, adjusted metabolic associated fatty liver disease (MAFLD) criteria<1 component, and adjusted MAFLD criteria<2 components. The prevalence of MHO/O and its relationship with the changes of body mass index (BMI), and the differences of the characteristics of MHO/O among the 7 types of metabolic health standards were compared. Result: The prevalence of MHO/O according to the ATP-Ⅲ (with WC)<1, ATP-Ⅲ (with WC)<2, ATP-Ⅲ (with WC)<3, ATP-Ⅲ (without WC)<1, ATP-Ⅲ (without WC)<2, adjusted MAFLD criteria<1, and adjusted MAFLD criteria<2 was 2.85%, 15.48%, 39.87%, 8.00%, 33.66%, 2.33%, 12.24%, respectively. The prevalence of MHO/O decreased as BMI increased. When BMI ≥ 28 kg/m2, the prevalence of MHO/O by ATP-Ⅲ (with WC)<1 and adjusted MAFLD criteria<1 dropped to 0. Conclusion: The adjusted MAFLD criterion without abnormal metabolic components is the most practicable definition of MHO/O.

Population genetic structure of critically endangered salamander (Hynobius amjiensis) in China: recommendations for conservation.

Amji's salamander (Hynobius amjiensis) is a critically endangered species (IUCN Red List), which is endemic to mainland China. In the present study, five haplotypes were genotyped for the mtDNA cyt b gene in 45 specimens from three populations. Relatively low levels of haplotype diversity (h = 0.524) and nucleotide diversity (π = 0.00532) were detected. Analyses of the phylogenic structure of H. amjiensis showed no evidence of major geographic partitions or substantial barriers to historical gene flow throughout the species' range. Two major phylogenetic haplotype groups were revealed, and were estimated to have diverged about 1.262 million years ago. Mismatch distribution analysis, neutrality tests, and Bayesian skyline plots revealed no evidence of dramatic changes in the effective population size. According to the SAMOVA and STRUCTURE analyses, H. amjiensis should be regarded as two different management units.

Polymorphic microsatellite loci isolated from Cervus unicolor (Cervidae) show inbreeding in a domesticated population of Taiwan Sambar deer.

Primers for eight microsatellites were developed; they successfully amplified DNA from 20 domesticated Formosan Sambar deer (Cervus unicolor swinhoei). All loci were polymorphic, with 10-19 alleles per locus. The average observed heterozygosity across loci and samples was 0.310, ranging from 0 to 0.750 at each locus. All loci but one, CU18, deviated from Hardy-Weinberg equilibrium due to excessive homozygosity in these domesticated broodstocks, reflecting inbreeding. These microsatellite loci will be useful, not only for assessment of population structure and genetic variability, but also for conservation of wild deer populations in Taiwan.

Population structure and demographic history of Sicyopterus japonicus (Perciformes; Gobiidae) in Taiwan inferred from mitochondrial control region sequences.

The amphidromous goby Sicyopterus japonicus is distributed throughout southern Taiwan and Japan. Larvae of this freshwater fish go through a long marine stage. This migratory mode influences population genetic structure. We examined the genetic diversity, population differentiation, and demographic history of S. japonicus based on the mitochondrial DNA control region. We identified 102 haplotypes from 107 S. japonicus individuals from 22 populations collected from Taiwan and Islet Lanyu. High mean haplotype diversity (h = 0.999) versus low nucleotide diversity (θπ = 0.008) was detected across populations. There was low correspondence between clusters identified in the neighbor-joining tree and geographical region, as also indicated by AMOVA and pairwise F(ST) estimates. Both mismatch distribution analysis and Tajima's D test indicated that S. japonicus likely experienced a demographic expansion. Using a Bayesian skyline plot approach, we estimated the time of onset of the expansion of S. japonicus at 135 kyr (during the Pleistocene) and the time of stable effective population size at approximately 2.5 kyr (last glacial maximum). Based on these results, we suggest 1) a panmictic population at the oceanic planktonic larval stage, mediated by the Kuroshio current; 2) a long planktonic marine stage and long period of dispersal, which may have permitted efficient tracking of environmental shifts during the Pleistocene; and 3) a stable, constant population size ever since the last glacial maximum.

Human umbilical cord Wharton's jelly stem cells and its conditioned medium support hematopoietic stem cell expansion ex vivo.

Bone marrow mesenchymal stromal cells (BMMSCs) have been used as feeder support for the ex vivo expansion of hematopoietic stem cells (HSCs) but have the limitations of painful harvest, morbidity, and risk of infection to the patient. This prompted us to explore the use of human umbilical cord Wharton's jelly MSCs (hWJSCs) and its conditioned medium (hWJSC-CM) for ex vivo expansion of HSCs in allogeneic and autologous settings because hWJSCs can be harvested in abundance painlessly, are proliferative, hypoimmunogenic, and secrete a variety of unique proteins. In the presence of hWJSCs and hWJSC-CM, HSCs put out pseudopodia-like outgrowths and became highly motile. Time lapse imaging showed that the outgrowths helped them to migrate towards and attach to the upper surfaces of hWJSCs and undergo proliferation. After 9 days of culture in the presence of hWJSCs and hWJSC-CM, MTT, and Trypan blue assays showed significant increases in HSC numbers, and FACS analysis generated significantly greater numbers of CD34(+) cells compared to controls. hWJSC-CM produced the highest number of colonies (CFU assay) and all six classifications of colony morphology typical of hematopoiesis were observed. Proteomic analysis of hWJSC-CM showed significantly greater levels of interleukins (IL-1a, IL-6, IL-7, and IL-8), SCF, HGF, and ICAM-1 compared to controls suggesting that they may be involved in the HSC multiplication. We propose that cord blood banks freeze autologous hWJSCs and umbilical cord blood (UCB) from the same umbilical cord at the same time for the patient for future ex vivo HSC expansion and cell-based therapies.

Effects of long-acting release octreotide on glucose homeostasis in acromegaly patients after trans-sphenoidal surgery.

The present study was aimed to investigate glucose homeostasis and insulin secretion in acromegalic patients during octreotide-long acting release (LAR) therapy and designed as an observational prospective study. 18 acromegalic patients who had undergone trans-sphenoidal surgery with active disease were included. All patients were treated with octreotide-LAR injection for 1 year. These patients received oral glucose tolerance test (OGTT) before, 21 days after, and 1 year after octreotide-LAR treatment. Primary outcomes were changes in glucose levels and insulin secretion during an OGTT. We also determined the differences between subjects with normalized and uncontrolled IGF-1 levels. Of the 18 patients treated with octreotide-LAR for 1 year, 89% achieved fasting GH levels <2.5 µg/l, 85% reached the nadir GH concentration <1 µg/l, and 61% achieved normal age- and sex-matched IGF-1 values. 21 days after one dose of octreotide-LAR injection, insulin response during OGTT significantly decreased, and the Matsuda index increased significantly. One year after octreotide-LAR therapy, most parameters of glucose homeostasis returned to baseline levels. However, insulin response during OGTT at 30 and 60 min, and the insulinogenic index were still significantly decreased. Compared with the IGF-1-normalized group, the IGF-1 uncontrolled group had the same fasting GH and nadir GH levels and a higher insulin AUC and total insulin secretion. During octreotide-LAR treatment, the early-phase insulin response to OGTT is reduced and plasma glucose levels remained normal in most patients. The IGF-1 uncontrolled group had the same fasting GH and nadir GH levels during OGTT, but had better glucose homeostasis.

Isolation and characterization of microsatellite markers for the White Cloud Mountain minnow (Tanichthys albonubes) in wild and cultured populations.

We developed 12 microsatellite loci for the endangered minnow species, Tanichthys albonubes, using PCR-based isolation of microsatellite arrays. These new markers were tested in 26 individuals from a wild population collected from Guangzhou in China and 26 individuals from a cultured strain. The number of alleles ranged from two to nine and the expected heterozygosity from 0.177 to 0.853. The wild population had significantly higher allelic richness than the cultured strain, with a mean allelic richness of 5.52 (range = 3.69-8.64) and 3.13 (range = 1.99-5.73) for the wild population and the cultured strain, respectively. No evidence of a recent bottleneck was detected in the wild population, but it was found in the cultured strain based on the BOTTLENECK test. These primers can be used to understand the demography and to examine genetic differences between the cultured T. albonubes strains and wild populations to help determine conservation and reintroduction strategies.

Multiple factors have shaped the phylogeography of Chinese spiny loach Cobitis sinensis in Taiwan as inferred from mitochondrial DNA variation.

Mitochondrial DNA cytochrome b sequences (1140 bp) in 61 specimens of Chinese spiny loach Cobitis sinensis from 12 drainages in Taiwan were identified as two major clades, exhibiting a southern and a northern distribution, north of TzengWen and south of TzengWen (including TzengWen), respectively. The divergence time between these two phylogroups was estimated at 7.34-9.06 million years before present (B.P.), but these two phylogroups were formed c. 3.41-4.23 and 2.22-2.75 M B.P., respectively. Moreover, geological events have been recalculated that Taiwan Island emerged above sea level at an estimate of c. 4-5 M B.P., and quickly became its present shape at c. 2 M B.P. through mountain building. These results suggest that these two major clades of C. sinensis in Taiwan might originate from two different continental populations, since the island's initial isolation in the Pliocene. Within southern Taiwan, the initial colonization was hypothesized to be in KaoPing River, followed by its northward dispersal. The high divergence between KaoPing and TzengWen was influenced by glaciations and landforms. Within north Taiwan, the colonization was from the Miaoli Plateau through western Taiwan to north-eastern and northern Taiwan. This dispersal pattern is concordant with the previously proposed hypothesis. Apparently, both geological and phylogeographic evidence suggested that river capture of the upper Takia River by the LanYang River promoted range expansion in freshwater fishes and also indicated that the Central Range within Taiwan did not act as a barrier to the dispersal of C. sinensis.

Comparative analysis of protein expression in differentiated thyroid tumours: a multicentre study.

This study compared clinical features and protein expression profiles in differentiated thyroid tumours to identify protein markers with the potential for indicating malignancy status. Tissue microarrays were constructed using 119 thyroid tumour samples (45 papillary carcinomas, 26 follicular carcinomas, 48 adenomas). Generally, there was overexpression of proliferating cell nuclear antigen (PCNA), p53, matrix metalloproteinase (MMP)-7, Hector Battifora mesothelial-1 (HBME-1), MMP-2, pituitary tumour-transforming gene (PTTG) and human telomerase reverse transcriptase (hTERT) in malignant thyroid carcinomas, and overexpression of fragile histidine triad (FHIT), p16 and E-cadherin in thyroid adenomas. Multiple factor binary logistic regression analysis indicated that MMP-2, HBME-1, p16 and FHIT were independently related to differentiated thyroid tumours. Receiver-operating characteristics for these four factors showed HBME-1 as best for diagnostic accuracy. Sensitivity and specificity were enhanced using an HBME-1 and p16 cluster. HBME-1 expression was not significantly different for papillary and follicular carcinomas, whereas p16 expression was significantly specific.

Thermoregulatory sudomotor dysfunction and diabetic neuropathy develop in parallel in at-risk feet.

AIMS: To establish the longitudinal relationship of foot complications to neuropathy based on a 4-year follow-up of diabetic patients stratified by sudomotor dysfunctions. METHODS: One hundred and nineteen Type 2 diabetic patients and 36 non-diabetic subjects were initially registered in the prospective cohort study. Plantar skin temperature and sympathetic skin response (SSR) were used to monitor sympathetic mediated thermoregulation and sudomotor function. Peripheral somatic and central autonomic functions were studied using clinical, nerve conduction and cardiovascular reflex tests. At enrolment, the diabetic patients were classified into one of three groups by the progressive stages of sudomotor dysfunction: SSR+ (SSR present; 49 patients), SSR- (SSR absent; 41 patients) and at-risk group (SSR absent but with cracked skin involving partial thickness of the dermis; 29 patients). RESULTS: The at-risk group had 13.4 times (95% confidence interval 1.4-125.7) higher plantar ulceration rates than the other two patient groups during the 4 years. Skin temperature elevation occurred in parallel with development of foot sweating problems. There were no significant differences between the three patient groups in the ratios of abnormal heart rate variation, orthostatic test and clinical neuropathy score at follow-up. After 4 years of follow-up, nerve conduction abnormalities were more frequent in the at-risk and SSR- groups than in the SSR+ group. CONCLUSIONS: Early deterioration of small sympathetic fibres could not be quantified accurately by the clinical, somatic and autonomic tests. Assessing skin integrity and sudomotor function in at-risk individuals identifies early peripheral sympathetic neuropathy, even if the patients have no overt clinical symptoms.

Improvement of glycaemia control in subjects with type 2 diabetes by self-monitoring of blood glucose: comparison of two management programs adjusting bedtime insulin dosage.

AIM: Self-monitoring of blood glucose (SMBG) is important for patients treated with insulin to detect asymptomatic hypoglycaemia and to guide patients towards reaching blood glucose goal. This study compared two management programs for adjusting bedtime insulin dose: program 1 (performed by study subjects) vs. program 2 (performed by study subjects and reminded by investigators). METHODS: This is a prospective, open-level, 28-week randomized trial in poorly controlled type 2 diabetic subjects. One hundred subjects treated with oral antidiabetic drugs plus bedtime insulin with glycated haemoglobin A(1C) (A1C) >8.0% were screened and received a structure education package in a 4-week run-in period. Seventy-eight subjects were randomized to two treatment programs (adjust insulin dose by themselves with or without investigators' reminder) and reviewed by the investigators at a 4-week interval clinical visit. RESULTS: The mean SMBG decreased significantly in both groups, with a greater decrease observed in program 2 vs. program 1 (from 198.7 +/- 43.1 to 122.6 +/- 21.9 mg/dl vs. from 194.0 +/- 42.7 to 151.6 +/- 37.7 mg/dl, p < 0.001). Bedtime insulin dose increased in both groups with a greater increase in program 2 (from 14.4 +/- 8.7 to 27.4 +/- 12.8 IU vs. from 14.3 +/- 8.3 to 18.4 +/- 6.2 IU, p < 0.001). There was a significant reduction in A1C from 9.54 +/- 1.67% to 7.76 +/- 1.27%, with a greater decrease (p < 0.001) in program 2 (2.17%) than in program 1 (1.40%). There were more subjects in the program 2 group achieving the treating targets: mean SMBG < or =120 mg/dl (46.9 vs. 17.9%) and A1C < or =7.0% (54.5 vs. 32.2%). There was no significant difference in the incidence of hypoglycaemia and body weight changes. CONCLUSIONS: Systematically titrating bedtime insulin dose added to oral therapy, especially combined with health care reminders, can safely improve glycaemic control in type 2 diabetes with poor glycaemic control. This regimen may facilitate safe and effective insulin therapy in routine medical practice and improve achievement of recommended standards of diabetes care.

I148M variant of PNPLA3 increases the susceptibility to non-alcoholic fatty liver disease caused by obesity and metabolic disorders.

BACKGROUND: The patatin-like phospholipase 3 (PNPLA3) rs738409 gene polymorphism is an important genetic determinant of non-alcoholic fatty liver disease (NAFLD). However, the associations between liver fat and metabolic traits in rs738409 G allele carriers and the allelic influence on this association have not been fully studied. AIM: To investigate the influence of the PNPLA3 gene polymorphism on the association of liver fat with serum metabolic factors and carotid atherosclerosis. METHODS: Liver fat was measured by quantitative ultrasound in 4300 subjects in the Shanghai Changfeng community and analysed for its association with obesity and metabolic factors in individuals with the PNPLA3 CC, CG and GG genotypes. RESULTS: Non-alcoholic fatty liver disease occurred in 37.9% and 28.8% of the subjects with the GG and CC genotypes respectively (P < 0.001). Liver fat was significantly associated with body mass index, waist circumference, serum triglycerides, high-density lipoprotein cholesterol, fasting blood glucose and insulin in the PNPLA3 rs738409 G allele carriers (P < 0.001). Compared with the CC homozygotes, the GG homozygotes presented higher liver fat and liver fibrosis scores despite their better metabolic status (comparison of regression line slopes, P < 0.05). An increase in liver fat was accompanied by a significant increase in the average and maximum carotid intima-media thickness in subjects with the PNPLA3 CC genotype but not in those with the GG genotype. CONCLUSIONS: PNPLA3 rs738409 G allele carriers were found to be more susceptible to the metabolic-related hepatic steatosis, and developed NAFLD and liver fibrosis despite presenting relatively better metabolic statuses and lower risks for carotid atherosclerosis.

Treatment of recurrent thyroid cysts by injection of tetracycline or minocycline.

We analyzed the effects of tetracycline hydrochloride or minocycline hydrochloride sclerotherapy on 66 recurrent thyroid cysts. All were hemorrhagic lesions except one serous cyst; cytologic study showed all were benign. On average, three treatments were given until resolution or the patient became unavailable for follow-up. The cumulative frequency of cyst disappearance was 33%, 45%, 52%, and 59% after 1, 2, 3, and 4 treatments. Five additional patients had cyst resolution after six to 19 treatments, and the serous lesion did not resolve. Cysts requiring more than two treatments were larger at presentation than those resolving after one or two treatments. Side effects in 179 treatments were local pain lasting ten to 20 minutes in 4.5%, radiated pain lasting one to two hours in 4.5%, fatigue lasting one to two days in 3.9%, and a febrile sensation lasting one to two days in 2.8%. Hemorrhagic thyroid cysts can usually be cured by repeated tetracycline or minocycline sclerotherapy with tolerable side effects.

Multiple forms of human pancreatic growth hormone releasing factor-like immunoreactivity in teleost brain and pituitary.

Two anatomically distinct neuronal GRF systems in the brain-pituitary of the teleost codfish (Gadus morhua), immunohistochemically localized by use of antisera directed against hpGRF1-44NH2 and hpGRF1-40OH are described. Chromatographic analysis additionally revealed the presence of three molecular variants of immunoreactive hpGRF1-44NH2, two of which differ from the authentic human material. However, all three forms released GH from rat pituitary cells in dispersed culture. These findings indicate that hpGRF is highly conserved in nature and suggest that peptides closely related to this human hypothalamic releasing hormone regulate the teleost pituitary.

Immunoreactive growth hormone-releasing factor in human stalk median eminence.

Immunoreactive growth hormone-releasing factor was detected in extracts of acetone preserved human stalk median eminence utilizing an antiserum against human GRF-(1-44)-NH2, isolated from a pancreatic tumor. The antibody is highly specific for the C-terminus of GRF-(1-44)-NH2, and has a cross-reactivity less than 0.02% with GRF-(1-40) free acid, a peptide isolated from a different pancreatic tumor. The mean concentration of IR-GRF in 5 pools of 10-15 stalk-median eminence fragments was 57.7 +/- 7.2 ng/mg protein (mean +/- SEM, range 42.5-75.8 ng/mg protein). Gel filtration chromatographic analysis showed that 97% of the IR-GRF coeluted with synthetic hpGRF-(1-44)-NH2 and eluate inhibition of binding in the radioimmunoassay was parallel to that of hpGRF-(1-44)-NH2. These data strongly suggest that human hypothalamic tissue contains a peptide that is similar to hpGRF-(1-44)-NH2.

A point mutation in the albumin gene in a Chinese patient with familial dysalbuminemic hyperthyroxinemia.

Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant disorder characterized by euthyroid hyperthyroxinemia. However, FDH has not been reported in Chinese or African patients. Here, we report the first case of FDH in a Chinese patient. A 69-year-old Chinese man was found to have increased serum total T(4) concentrations (198-242nmol/l; normal range 58-148nmol/l) and free T(4) concentrations (>58pmol/l; T(4) analog method, normal range 9-28pmol/l). Serum total T(3) and TSH concentrations were normal. The patient was misdiagnosed as hyperthyroid and was later suspected to have a TSH-producing tumor by the finding of a pituitary microadenoma, which was eventually proven to be a non-functional pituitary 'incidentaloma'. Electrophoretic analysis of the patient's serum proteins demonstrated enhanced albumin binding of [(125)I]T(4). Serum free T(4) concentrations were normal (16-19pmol/l, normal range 9-26pmol/l) when a two-step method was used. Direct sequencing of the albumin gene showed a guanine to adenosine transition in the second nucleotide of codon 218, resulting in a substitution of histidine (CAC) for the normal arginine (CGC) in one of the two alleles in the patient. The point mutation was further confirmed by HphI digestion of exon 7 of the albumin gene. The patient's son was not affected. Our studies demonstrated that the point mutation of the albumin gene in a Chinese patient with FDH was similar to that found in western white families, but differed from that in a Japanese family in whom a guanine to cytosine transition at the same position was found.

Immunocytochemical demonstration of growth hormone-releasing factor in gastrointestinal and pancreatic endocrine tumors.

Growth hormone-releasing factor (GRF), a linear peptide that exists in a number of different molecular forms (GRF-44, -40, -37, and-31) has been shown to be responsible for the acromegaly associated with certain endocrine tumors of the pancreas and other foregut-derived structures. With the use of two anti-sera (#1A850 and G59/901) directed against different segments of the GRF molecule, a series of 24 pancreatic and 35 gastrointestinal endocrine tumors, not associated with acromegaly, were surveyed systematically for immunocytochemical localization of GRF in the tumor cells. Strong immunoreactivity for GRF was encountered in 10 tumors (6 pancreatic and 4 gastrointestinal). While all ten tumors were immunoreactive against G59/901, which recognizes GRF-44, -40, and -37, two jejunal carcinoids showed additional immunostaining with 1A850 that is specific for GRF-44. Seven of these ten tumors were also immunoreactive for a variety of other regulatory peptides and neurotransmitters, including gastrin, insulin, glucagon, serotonin, substance P, somatostatin, pancreatic polypeptide, vasoactive intestinal peptide (VIP), and adrenocorticotropic hormone (ACTH). No consistent pattern of association between GRF and the other regulatory substances was evident. These findings indicate that, even in the absence of associated acromegaly, up to 17% of endocrine tumors of the gastro-entero-pancreatic (GEP) axis show immunoreactivity for GRF and that such reactivity is associated more frequently with pancreatic (25%) than with gastrointestinal (11%) endocrine tumors.

Topographical and ontogenetic study of the neurons producing growth hormone-releasing factor in human hypothalamus.

Neurons producing growth hormone-releasing factor have been characterized and analyzed by immunohistochemistry in the hypothalami of human fetuses, neonates, infants and adults, using two antibodies against human pancreatic GRF (hpGRF). One of the antibodies recognized both the hpGRF(1-40)OH and hpGRF(1-44)NH2 in the mid portion (between the 28th and 39th amino acid), the other one specifically recognized the C-terminal end of hpGRF(1-44)NH2. These two antibodies stain a single neuronal system with cell bodies mainly located in the infundibular (arcuate) nucleus, and in the ventromedial and lateralis tuber nuclei. These neurons project to the median eminence where they give numerous endings in contact with portal vessels. These neurons are distinct from those containing LH-RH, somatostatin, CRF or pro-opiocortin. In fetuses, neurons immunoreactive with hpGRF antibodies are first detected at the 29th week. They display a neuroblastic aspect which persists after birth. Immunoreactive fibers are detectable in the median eminence after the 31st week. These results demonstrate that the infundibular nucleus plays a major role in control of GH secretion in man and that secretion of GRF appears late during fetal life; this suggests that the first stages of differentiation and development of GH producing cells in the human fetus do not depend on hypothalamic GRF secretion.