Effects of IL-1 on hematopoietic progenitors after myelosuppressive chemoradiotherapy

Recently it has been recognized that IL-1 plays an important role in hematopoietic regulation. Administration of 5-fluorouracil (5-FU) to mice causes prolonged neutropenia. rHIL-1 injected to mice after 5-FU, accelerated the recovery of hematopoietic progenitors and blood neutrophils. The combination of rhIL-1 and rhG-CSF reduced the neutropenic period significantly. Sublethal irradiation of mice induced profound neutropenia for 3 weeks which was associated with 80% mortality. Administration of rhIL-1 20 hours prior to or 2 hours post irradiation resulted in a significantly improved survival and rapid recovery of the neutrophil count. IL-1 administered alone or in combination with other colony stimulating factors to spontaneous breast tumor bearing mice following 5-FU therapy resulted in a rapid recovery of neutrophils, improved survival, and markedly reduced the tumor mass. Experiments in primates demonstrated that rhIL-1 administered to 5-FU treated animals shortened the neutropenic period from 30 to 17 days and increased the number of marrow progenitors responsive to other CSFs. Prolonged administration of IL-1 (14 days) to these animals resulted in a delayed neutrophil recovery as compared to animals receiving short courses of IL-1. rhIL-1 administered to primates receiving marrow grafts after lethal irradiation, did not result in rapid hematopoietic recovery. In humans, studies with CD-34 positive marrow cells showed that IL-1 had a radioprotective effect on a committed and early marrow progenitors. These data show the therapeutic potential of IL-1 in the treatment of chemoradiotherapy induced myelosuppression.     

Making our diabetes patients' office visits more productive

Improving our health care procedures is ideally a collaborative and ongoing process, yet it takes time we may not feel we can easily afford. If we can consider how we might make even one change to improve our procedures, we might also be able to help improve not only the capabilities and skills of each member of our health care teams but also the ability of our patients to engage in effective diabetes self-care.     

Microbiological quality of tomato (<i>Solanum lycopersicum</i> L.) produced under greenhouse conditions in five Municipalities of the State of Mexico

The aim of the current research was to determine tomato (Solanum lycopersicum L.) microbiological quality produced under greenhouse conditions in 5 municipalities of the State of Mexico. Studies were conducted during the 2013 production cycle to know the risks and apply prevention strategies prior to its consumption. A microbiological analysis of samples of irrigation water, soil and 100 tomato fruits variety cid was performed to determine Aerobic Mesophiles, Total Coliforms and Fecal Coliforms. The methodology used were those according to the Official Mexican Standards NOM- 109-SSA1-1994, NOM-110-SSA1-1994, NOM-092-SSA1-1994, NOM-113-SSA1-1994, and the Regulations of the National French Organization for Standardization (AFNOR) NF V08-60, and NOM-093-SSA1-1994, which establish the allowable limits for the study microorganisms. The results showed a zero level of pollution in water and soil samples. For fruits, levels of Aerobic Mesophilic were within the maximum limits permitted by the standards. The municipality of Texcaltitlan showed the highest average for these microorganisms (10083.80 CFU/mL). Huixquilucan showed 2266.84 CFU/mL for Total Coliforms. For Fecal Coliforms, municipalities of Coatepec and Texcaltitlan exceeded the allowed limit.     

Clinical phenotype, prognosis and mitochondrial DNA mutation load in mitochondrial encephalomyopathies

We studied 42 individuals, including 8 patients with either complete or partial syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), 8 patients with either complete or partial syndrome of myoclonic epilepsy with ragged-red fibers (MERRF) and 26 maternal family members who carried either the A3243G or A8344G mutation of mitochondrial DNA (mtDNA). Clinical manifestations and prognosis were followed up in the patients harboring the A3243G or A8344G mutation. The relationship between clinical features and proportions of mutant mtDNAs in muscle biopsies, blood cells and/or hair follicles was studied. In the 8 regularly followed patients with the A3243G mutation, 4 died within 1 month to 7 years due to status epilepticus and/or recurrent stroke-like episodes. Two patients developed marked mental deterioration and 2 remained stationary. All of the patients harboring the A8344G mutation were stable or deteriorated slightly, except for 1 patient who died due to brain herniation after putaminal hemorrhage. The A3243G and A8344G mtDNA mutations were heteroplasmic in the muscle biopsies, blood cells and hair follicles of both the probands and their maternal family members. The mean proportion of A3243G mutant mtDNA in the muscle biopsies of the patients with MELAS syndrome (68.5 ± 21.3%, range 33–92%) was significantly higher than that of the asymptomatic family members (37.1 ± 12.6%, range 0–51%). The average proportions of A8344G mutant mtDNA in the muscle biopsies (90.1 ± 3.9%, range 89–95%) and hair follicles (93.9 ± 6.4%, range 84–99%) of the patients with MERRF syndrome were also significantly higher than those of the asymptomatic family members (muscle: 40.3 ± 39.5%, range 1–80%; hair follicles: 51.0 ± 44.5%, range 0.1–82%). We concluded that measurement of the proportion of mutant mtDNA in muscle biopsies may provide useful information in the identification of symptomatic patients with mitochondrial encephalomyopathies. For patients with the A3243G mutation, the prognosis was related to status epilepticus and the number of recurrent stroke-like episodes and was much worse than for patients with the A8344G mutation of mtDNA, who had stable or slowly deteriorating clinical courses.     

Relationship between enzymatic activity and oligomerization state of tyrosine hydroxylase

The native form of tyrosine hydroxylase (TH) is a homotetramer which consists of four identical subunits each with an MW of approximately 60 kD. The relationships between the catalytic activity of TH and oligomerization of the enzyme have not yet been characterized. We have investigated, by deletion and/or substitution mutagenesis, the involvement of the leucine zipper (LZ) motifs in the oligomer formation of TH and its relation to catalytic activity. Our results demonstrate that deletion of the carboxyl-terminal LZ (LZ-C) abolishes tetramer formation. Interruption of the other two LZ motifs (LZ-A and LZ-B), located in a central region of the catalytic domain by substitution of Leu to Pro at residues 294 and 301 or 386 and 393 has no effect on the tetramer formation of TH. However, the interruption of LZ-A and LZ-B abolishes TH enzymatic activity. The substitution of Leu residues 188 and 190 with Pro at the regulatory domain of TH reduces enzymatic TH activity without affecting tetramer formation. Thus, LZ-C is required for tetramer formation, while LZ-A and LZ-B seem to be involved in the catalytic activity without affecting the tetramer formation of TH.     

ACUTE EFFECTS OF MOVEMENT VELOCITY ON BLOOD LACTATE AND GROWTH HORMONE RESPONSES AFTER ECCENTRIC BENCH PRESS EXERCISE IN RESISTANCE-TRAINED MEN

This study aimed to compare the effects of different velocities of eccentric muscle actions on acute blood lactate and serum growth hormone (GH) concentrations following free weight bench press exercises performed by resistance-trained men. Sixteen healthy men were divided into two groups: slow eccentric velocity (SEV; n = 8) and fast eccentric velocity (FEV; n = 8). Both groups performed four sets of eight eccentric repetitions at an intensity of 70% of their one repetition maximum eccentric (1RMecc) test, with 2-minute rest intervals between sets. The eccentric velocity was controlled to 3 seconds per range of motion for SEV and 0.5 seconds for the FEV group. There was a significant difference (P < 0.001) in the kinetics of blood lactate removal (at 3, 6, 9, 15, and 20 min) and higher mean values for peak blood lactate (P = 0.001) for the SEV group (9.1 ± 0.5 mM) compared to the FEV group (6.1 ± 0.4 mM). Additionally, serum GH concentrations were significantly higher (P < 0.001) at 15 minutes after bench press exercise in the SEV group (1.7 ± 0.6 ng · mL⁻¹) relative to the FEV group (0.1 ± 0.0 ng · mL⁻¹). In conclusion, the velocity of eccentric muscle action influences acute responses following bench press exercises performed by resistance-trained men using a slow velocity resulting in a greater metabolic stress and hormone response.     

Recent advances in genetic research on schizophrenia

Evidence for genetic factors in schizophrenia is reviewed with regard to family, twin and adoption studies, and recent advances in molecular genetic technology are applied to explore possible gene loci susceptible to schizophrenia. Application of neuropsychological and neuroimaging methodologies are also reviewed with an aim to develop criteria for defining phenotypes for genetic studies.Plenary Session, Twelfth Joint Annual Conference of Biomedical Sciences, April 20, 1997, Taipei, Taiwan.