Microanatomy of facial vibrissae in the Florida manatee: the basis for specialized sensory function and oripulation.

Sirenians, including Florida manatees, possess an array of hairs and bristles on the face. These are distributed in a pattern involving nine distinct regions of the face, unlike that of any other mammalian order. Some of these bristles and hairs are known to be used in tactile exploration and in grasping behaviors. In the present study we characterized the microanatomical structure of the hair and bristle follicles from the nine regions of the face. All follicles had the attributes of vibrissae, including a dense connective tissue capsule, prominent blood sinus complex, and substantial innervation. Each of the nine regions of the face exhibited a distinct combination of these morphological attributes, congruent with the previous designation of these regions based on location and external morphological criteria. The present data suggest that perioral bristles in manatees might have a tactile sensory role much like that of vibrissae in other mammals, in addition to their documented role in grasping of plants during feeding. Such a combination of motor and sensory usages would be unique to sirenians. Finally, we speculate that the facial hairs and bristles may play a role in hydrodynamic reception.     

Action and localization of neuropeptide Y in the human fallopian tube

Using indirect immunohistochemistry, neuropeptide Y-like immunoreactivity was found in nerve fibers around blood vessels and in the muscle layers of the human fallopian tube. Apart from a network of immunoreactive nerve fibers in connection with the luminary epithelium of the isthmus, the distribution resembled that of adrenergic, tyroxine hydroxylase immunoreactive, nerve fibers. Neuropeptide Y was found to have a dose-dependent inhibitory action on the adrenergic contractile response to field stimulation in the external longitudinal muscle layer of the isthmus. Furthermore, neuropeptide Y inhibited [3H]noradrenaline release from isthmic preparations during field stimulation, suggesting a prejunctional inhibitory action on adrenergic neurotransmission.     

Attenuated processing of proglucagon and glucagon-like peptide-1 in carboxypeptidase E-deficient mice

The maturation of many peptide hormones is attenuated in carboxypeptidase E (CPE)-deficient fat/fat mice, leading to a slowly developing, adult-onset obesity with mild diabetes. To determine the contribution of the hormones generated from the proglucagon precursor to this phenotype, we studied the tissue-specific processing of glucagon and glucagon-like peptide-1 (GLP-1) in these mice. In all tissues examined there was a great reduction in mature amidated GLP-1. Furthermore, a lack of CPE attenuates prohormone convertase processing of proglucagon in both the pancreas and the intestine. These findings suggest that defects in proglucagon processing together with other endocrine malfunctions could contribute to the diabetic and obesity phenotype in fat/fat mice.     

The diversity of dolichol-linked precursors to Asn-linked glycans likely results from secondary loss of sets of glycosyltransferases

The vast majority of eukaryotes (fungi, plants, animals, slime mold, and euglena) synthesize Asn-linked glycans (Alg) by means of a lipid-linked precursor dolichol-PP-GlcNAc2Man9Glc3. Knowledge of this pathway is important because defects in the glycosyltransferases (Alg1-Alg12 and others not yet identified), which make dolichol-PP-glycans, lead to numerous congenital disorders of glycosylation. Here we used bioinformatic and experimental methods to characterize Alg glycosyltransferases and dolichol-PP-glycans of diverse protists, including many human pathogens, with the following major conclusions. First, it is demonstrated that common ancestry is a useful method of predicting the Alg glycosyltransferase inventory of each eukaryote. Second, in the vast majority of cases, this inventory accurately predicts the dolichol-PP-glycans observed. Third, Alg glycosyltransferases are missing in sets from each organism (e.g., all of the glycosyltransferases that add glucose and mannose are absent from Giardia and Plasmodium). Fourth, dolichol-PP-GlcNAc2Man5 (present in Entamoeba and Trichomonas) and dolichol-PP- and N-linked GlcNAc2 (present in Giardia) have not been identified previously in wild-type organisms. Finally, the present diversity of protist and fungal dolichol-PP-linked glycans appears to result from secondary loss of glycosyltransferases from a common ancestor that contained the complete set of Alg glycosyltransferases.     

Allogeneic haematopoietic cell transplantation for myelofibrosis in 30 patients 60-78 years of age

We analysed the results of haematopoietic cell transplantation (HCT) in 30 patients aged 60-78 (median 65) years, with primary myelofibrosis or myelofibrosis evolving from antecedent polycythaemia vera or essential thrombocythaemia. Donors were human leucocyte antigen (HLA)-identical siblings (N = 15) or unrelated individuals (N = 15). Various conditioning regimens were used, ranging from very low intensity (fludarabine plus 2 Gy total body irradiation) to high dose (busulfan plus cyclophosphamide). Stem cell sources were granulocyte colony-stimulating factor mobilized peripheral blood progenitor cells in 29 patients and marrow in one patient. Sustained engraftment was documented in 27 of 30 patients. Day -100 mortality was 13%. With a median follow-up of 22 (range 0·5 - 69) months, 3-year overall survival and progression-free survival were 45% and 40%, respectively. Currently, 13 patients are surviving. Seven patients died with disease progression at 0·5 -22 months, and 10 patients died from other causes at 1·5 -37.5 months after HCT. While the selection of older patients for transplantation was probably biased, the present results are encouraging. Motivated older patients with myelofibrosis without substantial comorbid conditions should be offered the option of allogeneic HCT.     

Altered control of gastric acid secretion in gastrin-cholecystokinin double mutant mice

BACKGROUND & AIMS: Three pathways control gastric acid secretion: the gastrin-enterochromaffin-like (ECL) cell axis, the vagus-parietal cell axis, and the cholecystokinin (CCK)-D cell axis. Mice lacking gastrin or both gastrin and CCK were examined to determine the role of the hormones. METHODS: Acid was measured after pylorus ligation, and biopsies from gastrin knockout (KO), gastrin-CCK double-KO, and wild-type (WT) mice were collected for biochemical, immunocytochemical, and electron-microscopic examination. RESULTS: The ECL cells were inactive in both groups of mutant mice but the cell number was unaffected. Both parietal cell number and level of H(+)/K(+)-ATPase messenger RNA (mRNA) were reduced in the mutant strains, but gastrin-CCK double-KO mice displayed more active parietal cells and larger acid output than the gastrin KO mice. The acid response to histamine in double-KO mice was unchanged whereas that to gastrin was diminished, but it could be restored by infusion of gastrin. Oxyntic D-cell density was the same in both mutant strains, but the D cells were more active in the gastrin KO than in the double-KO mice. CCK infusion in gastrin-CCK double-KO mice raised the somatostatin mRNA level and inhibited acid secretion to the level seen in gastrin KO mice. Vagotomy and atropine abolished acid secretion in all 3 groups of mice. CONCLUSIONS: Lack of gastrin impairs the gastrin-ECL axis, whereas lack of gastrin and CCK impairs both hormonal pathways. In the gastrin-CCK double-KO mice, acid secretion is only controlled by cholinergic vagal stimulation, which normalizes the acid output.     

Co-occurrence of Psychiatric Disorders and Alcoholism in Untreated Alcoholic Patients in a VA Medical Walk-in (Triage) Clinic Population

The authors identified 1,836 male veterans who were seeking treatment for various medical disorders at a walk-in (triage) clinic and screened these patients for the presence of alcohol problems by administering a brief interview and the CAGE questionnaire. Patients who screened positive for alcohol problems and who had little or no prior treatment for these problems were then interviewed using a structured psychiatric interview to establish the presence of alcohol dependence and co-occurring psychiatric disorders. The rate of alcohol dependence and co-occurring disorders was substantial, and the pattern was consistent with studies of veteran patients surveyed in other clinical settings.     

Growth factors and stromal support generate very efficient retroviral transduction of peripheral blood CD34+ cells from Gaucher patients

We have achieved high-efficiency gene transfer into nonmobilized peripheral blood (PB) CD34+ cells from patients with Gaucher's disease using a clinically acceptable retroviral supernatant transduction protocol. In our studies, bone marrow (BM) and PB CD34+ cells were transduced using a high titer (10(8) particles/mL) retroviral supernatant once a day for 4 consecutive days in the presence of interleukin-3 (IL-3), IL-6, and stem cell factor (SCF), with or without an irradiated allogeneic BM stromal layer. The growth factors alone resulted in 29% +/- 10% gene transfer of PB CD34+ clonogenic cells in contrast with 71% +/- 17% gene transfer efficiency using stroma with the growth factors; a 2.5-fold increase. The increase in gene transfer efficiency was less prominent when BM CD34+ cells were used (40% +/- 16% without and 57% +/- 8% with stroma, a 1.5-fold increase). The overall transduction efficiency of both PB and BM CD34+ cells was lower when the cells were transduced over a stromal cell layer without added growth factors. The combination of IL-3, IL-6, and SCF with stroma transduced 75% of primitive long-term culture initiating cells (PB LTC- ICs) in comparison with 34% of LTC-ICs when IL-3, IL-6, and SCF were used without stromal support. Using this clinically acceptable supernatant/cytokines/stroma transduction protocol, correction of the glucocerebrosidase (GC) deficiency in the progeny cells of PBLTC-ICs from Gaucher's-disease patients has been accomplished. Efficient transduction of the PB CD34+ cells using this transduction protocol may allow repeated delivery of "GC-corrected" hematopoietic stem and progenitor cells to Gaucher's-disease patients.     

Immunogenicity in infants of a vaccine composed of Haemophilus influenzae type b capsular polysaccharide mixed with DPT or conjugated to diphtheria toxoid

Fifty-three healthy infants received either Haemophilus influenzae type b capsular polysaccharide (PRP) mixed with diphtheria-pertussis-tetanus vaccine (DPT) or PRP conjugated covalently to diphtheria toxoid (PRP-D). The immunizations were given at 3, 5, 7, and either 14 or 18 months of age and were well tolerated. The geometric mean titers of antibody to PRP at eight months of age (after the first immunizations) were 0.26 micrograms/ml in the PRP + DPT group and 1.56 micrograms/ml in the PRP-D group. After the fourth dose, an IgG response was seen in both groups. The PRP + DPT group had a geometric mean level of antibody to PRP of 3.98 micrograms/ml at 19 months and the PRP-D group, 31.22 or 24.00 micrograms/ml at 15 or 19 months, respectively. Compared with previously published data of children immunized with one dose of PRP at 18 months, the mean level of antibody to PRP in the PRP-D group at 19 months was significantly (P less than .001) higher, whereas that in the PRP + DPT group was not.