Predictors of weight loss during radiation therapy.

OBJECTIVE: To define risk factors for weight loss or dehydration during radiation therapy (RT). STUDY DESIGN AND SETTING: Retrospective chart review, academic tertiary care center. RESULTS: The incidence of severe weight loss during RT was 32.7%, the incidence of dehydration was 10.9%, and the rate of prophylactic feeding gastrostomy tube placement was 32%. The patients most likely to suffer severe weight loss included patients with tumor sites of nasopharynx and base of tongue, those treated with chemoradiation, and patients with severe pretreatment weight loss. Prophylactic feeding gastrostomy tube placement before RT significantly reduced the incidence of severe weight loss and hospitalization during RT. CONCLUSION: Severe weight loss and dehydration during RT for head and neck cancer is common. Prophylactic feeding gastrostomy tubes significantly reduce the incidence of severe weight loss and hospitalization for dehydration during RT when placed before onset of RT. Patients at risk for severe weight loss include those with severe pretreatment weight loss, tumors of the nasopharynx and base of tongue, or treatment with chemoradiation.

The Drosophila GMII gene encodes a Golgi alpha-mannosidase II.

In this paper we show the organisation of the Drosophila gene encoding a Golgi alpha-mannosidase II. We demonstrate that it encodes a functional homologue of the mouse Golgi alpha-mannosidase II. The Drosophila and mouse cDNA sequences translate into amino acid sequences which show 41% identity and 61% similarity. Expression of the Drosophila GMII sequence in CHOP cells produces an enzyme which has mannosidase activity and is inhibited by swainsonine and by CuSO(4.) In cultured Drosophila cells and in Drosophila embryos, antibodies raised against a C-terminal peptide localise this product mainly to the Golgi apparatus as identified by cryo-immuno electron microscopy studies and by antibodies raised against known mammalian Golgi proteins. We discuss these results in terms of the possible use of dGMII as a Drosophila Golgi marker.

Selective neck dissections for squamous carcinoma of the upper aerodigestive tract: patterns of regional failure.

BACKGROUND: Surgeons have been using selective neck dissections in the treatment of squamous carcinoma of the upper aerodigestive tract for over 20 years. To date, no data is available that can answer the question "What are the patterns of failure in the neck following a selective neck dissection and is a selective neck dissection a reliable procedure for metastatic disease?" METHODS: To answer this question, the medical records of all patients with squamous carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx treated at The University of Texas M. D. Anderson Cancer Center from January 1, 1985-December 31, 1990, with a selective neck dissection were reviewed. Five hundred seventeen neck dissections were analyzed: suprahyoid (41), supraomohyoid (284), and anterolateral (192). The end point of the study was regional failure and survival. RESULTS: Regional recurrence in patients treated with a suprahyoid dissection was 43% with pathologically positive nodes. The regional recurrence in the patients treated with a supraomohyoid neck dissection was 1.9% with pathologically negative nodes, 35.7% with path N1 without postoperative radiation therapy, and 5.6% with postoperative radiation therapy. The neck staged pathologically N2B failed with and without postoperative radiation, 8.3% and 14%, respectively. Thirteen percent of the anterior/lateral neck dissections failed regionally. If multiple pathologically positive nodes (N2B) were present, the regional failure with postoperative radiation was 30% and 33.3% without postoperative radiation. CONCLUSION: The results of this retrospective study suggest that a selective neck dissection is a satisfactory staging procedure and is a definitive operation if all the nodes are pathologically negative. However, if a node is found to be invaded with cancer, the use of postoperative radiation is advisable.

Mutant analysis reveals an alternative pathway for N-linked glycosylation in Drosophila melanogaster.

The mas-1 gene of Drosophila melanogaster encodes Golgi mannosidase I (MAS-1), and flies homozygous for small deletions of the gene are viable. They show but few abnormalities and those have a low penetrance [Kerscher, S., Albert, S., Wucherpfennig, D., Heisenberg, M. & Schneuwly, S. (1995) Dev. Biol. 168, 613-626]. Here we sequence the N-linked oligosaccharides associated with a reporter protein, and with membrane proteins prepared from wild type and MAS-1 null organisms. The results show that the null organisms synthesise the same range of oligosaccharides as wild type, albeit with different ratios. There is an accumulation of the Man8GlcNAc2 which is one of the substrates for the MAS-1 enzyme. This supports the suggestion of Kerscher et al. that the lack of severe phenotypic disturbances in the null organisms is due to the presence of an alternative pathway(s), but it also shows that this alternative pathway(s) does not entirely compensate for the normal pathway.

The soluble alpha-mannosidases of Drosophila melanogaster.

The alpha-mannosidases are implicated in both the catabolism of carbohydrates and the N-linked glycosylation pathway in insects, but little is known of the biochemistry of these glycosidases. In order to study the soluble alpha-mannosidases of Drosophila melanogaster we have used artificial fluorogenic substrates for detection of activity in situ following non-denaturing gel electrophoresis. This approach also permitted examination of the mannosidases present in different tissues and the sensitivity of the enzymes to known mannosidase inhibitors. Fluorogenic substrates were also used to determine the pH optima of partly purified mannosidases. We report that D. melanogaster contains several soluble alpha-mannosidase activities. Acidic mannosidases were detected in the gut, fat body and haemolymph of third-instar larvae. The major activity detected in larval guts was a neutral mannosidase presumed to be involved in digestion.

Nucleotide sequence of a Drosophila melanogaster cDNA encoding a calnexin homologue.

A cDNA which encodes a calnexin (Cnx)-like protein from Drosophila melanogaster has been characterized. The deduced amino acid sequence shares several regions of homology with Cnx from other sources with two conserved motifs each repeated four times. The gene was found to be transcribed in various tissues and at all developmental stages. We have mapped the gene at chromosomal position 99A and we have also mapped the related gene coding for Drosophila calreticulin at 85E.

AGI, a previously unreported D. melanogaster alpha-glucosidase: partial purification, characterization, and cytogenetic mapping.

Inbred Drosophila melanogaster stocks were surveyed for alpha-glucosidases with nondenaturing gel electrophoresis using a fluorogenic substrate to stain the gels. The glucosidase most active under these conditions is polymorphic. We established that the polymorphism is genetic in origin and that the glucosidase was not likely to be a previously characterized enzyme. The gene encoding the enzyme was mapped cytogenetically to 33 A1-2- 33A8-B1, confirming that this is an enzyme not yet reported in D. melanogaster. The enzyme was partially purified by elution from nondenaturing gels, which enabled us to establish that it has optimal activity at pH 6 and interacts most strongly with alpha-1-4 glucosides. A developmental and tissue survey suggested that this enzyme could have a purely digestive role or be involved in carbohydrate metabolism inside the organism. We propose that this enzyme is involved in either starch digestion or glycogen metabolism.

Acemannan-containing wound dressing gel reduces radiation-induced skin reactions in C3H mice.

PURPOSE: To determine (a) whether a wound dressing gel that contains acemannan extracted from aloe leaves affects the severity of radiation-induced acute skin reactions in C3H mice; (b) if so, whether other commercially available gels such as a personal lubricating jelly and a healing ointment have similar effects; and (c) when the wound dressing gel should be applied for maximum effect. METHODS AND MATERIALS: Male C3H mice received graded single doses of gamma radiation ranging from 30 to 47.5 Gy to the right leg. In most experiments, the gel was applied daily beginning immediately after irradiation. To determine timing of application for best effect, gel was applied beginning on day -7, 0, or +7 relative to the day of irradiation (day 0) and continuing for 1, 2, 3, 4, or 5 weeks. The right inner thigh of each mouse was scored on a scale of 0 to 3.5 for severity of radiation reaction from the seventh to the 35th day after irradiation. Dose-response curves were obtained by plotting the percentage of mice that reached or exceeded a given peak skin reaction as a function of dose. Curves were fitted by logit analysis and ED50 values, and 95% confidence limits were obtained. RESULTS: The average peak skin reactions of the wound dressing gel-treated mice were lower than those of the untreated mice at all radiation doses tested. The ED50 values for skin reactions of 2.0-2.75 were approximately 7 Gy higher in the wound dressing gel-treated mice. The average peak skin reactions and the ED50 values for mice treated with personal lubricating jelly or healing ointment were similar to irradiated control values. Reduction in the percentage of mice with skin reactions of 2.5 or more was greatest in the groups that received wound dressing gel for at least 2 weeks beginning immediately after irradiation. There was no effect if gel was applied only before irradiation or beginning 1 week after irradiation. CONCLUSION: Wound dressing gel, but not personal lubricating jelly or healing ointment, reduces acute radiation-induced skin reactions in C3H mice if applied daily for at least 2 weeks beginning immediately after irradiation.

Cloning and sequence analysis of GmII, a Drosophila melanogaster homologue of the cDNA encoding murine Golgi alpha-mannosidase II.

Using the murine cDNA that encodes Golgi alpha-mannosidase II (GlcNAc transferase I-dependent alpha 1,3[alpha 1,6] mannosidase; EC 3.2.1.114) as a probe to screen a cDNA library made from Drosophila melanogaster (Dm) embryos, we have isolated GmII, the Dm sequence homologue. The 3926-bp cDNA has an open reading frame of 3327 bp and predicts a polypeptide of approx. 127 kDa, a mass similar to that of the murine protein. The deduced mouse and Dm amino acid (aa) sequences share extensive similarity across their entire lengths and are both type-II transmembrane (TM) proteins with short cytoplasmic tails, single TM domains and large hydrophilic C-terminal domains. A region of approx. 200 aa, within the C-terminal domain, has considerable similarity to a corresponding region from several other alpha-mannosidases. GmII has been localized to a single site (85D14-18) on the right arm of chromosome 3.

Interleukin-1 dose, mouse strain, and end point as they affect protection of mouse jejunum.

Interleukin 1 (IL-1) has been shown to protect a number of normal tissues against radiation injury. In mouse jejunum, modest protection against radiation injury has been reported using only the in vivo crypt survival assay in one mouse strain. The major goal of this study was to determine the protective effect of IL-1 on mouse jejunum using two assays of damage, crypt cell survival and lethality from radiation-induced crypt cell depletion, in two mouse strains, C3Hf/Kam and BALB/c nu/+, which were bred and maintained in a specific-pathogen-free barrier colony. In addition, the dependence of protection on the IL-1 dose in both assays was determined. Our findings showed that IL-1 protection of crypt cell depletion and subsequent death of the animals from loss of these cells was dependent on the IL-1 dose. We found that the amount of protection by IL-1 was related to the criterion used to assess the protection. For example, if protection was determined as a ratio of D10's or LD50/10, a bigger DMF was obtained for BALB/c mice than C3H mice with the same IL-1 dose, suggesting that C3H mice were not as well protected. However, if protection was determined by the increase in crypt cell number after IL-1, there was an identical 2.4-fold increase in crypt cells after the same IL-1 dose in both strains. On the basis of this criterion, then, protection of crypt cells by IL-1 did not depend on the mouse strain. Although the effect of IL-1 on animal survival at 10 days was strain dependent, the difference was related to differences in the slopes of the respective crypt cell survival curves for the two strains and not to different effects of IL-1 in the two strains tested.

Flexible casts used in making indirect interim restorations.

This article describes a procedure for making indirect interim restorations from a cast and dies made of polyvinyl siloxane impression material. The use of these flexible casts and dies facilitates the removal of the polymerized resin from the cast and the rapid set of the polyvinyl materials reduces the time involved in making the indirect interim restorations.

Detection of the lipid-linked precursor oligosaccharide of N-linked protein glycosylation in Drosophila melanogaster.

The presence of a glycan of the same molecular size as the lipid linked precursor oligosaccharide (Glc3Man9GlcNAc2) of the N-linked protein glycosylation pathway in mammalian cells has been detected in a glycolipid fraction of cultured Drosophila melanogaster cells. Oligosaccharide sequencing studies were consistent with the existence of a glucosylated high mannose containing structure, which may be the common precursor for N-linked protein glycosylation in insect cells.

The major serum protein of Drosophila larvae, larval serum protein 1, is dispensable.

Null alleles of all three genes (alpha, beta and gamma) coding for the major serum protein of Drosophila larvae, larval serum protein 1, have been characterized at the protein level and by analysis of their RNA and DNA. Each allele completely lacks one polypeptide chain. beta shows an unaltered gene but reduced levels of RNA, alpha shows restriction-fragment-length polymorphism and shows low levels of transcript, while gamma is a deletion. The three null alleles have been combined to give a strain without the gene for larval serum protein 1 which survives.

Necrotizing fasciitis of the vulva.

Sixteen cases of necrotizing fasciitis arising from or involving the vulva are presented. Fifteen of the 16 women had diabetes mellitus. Five of them died. All but one of these cases were managed by very extensive excision of all involved tissues. These cases demonstrate the extreme seriousness of any infection involving the vulva in a diabetic patient. Such patients should have the infected area explored while they are under anesthesia as soon as possible. If any necrosis is found, radical excision to include removal of all necrotic, indurated, and pale tissues is mandatory.

A Genetic and Cytogenetic Analysis of the Region Surrounding the Lsp-1 beta-Gene in DROSOPHILA MELANOGASTER.

The region surrounding the gene coding for the beta-polypeptide (21D-22C) of the major Drosophila melanogaster larval serum protein, LSP-1, has been studied in detail. Seven new gamma-ray-induced deficiencies of the region have been used, together with the two extant deficiencies, to map the position of the beta-gene and of the 55 newly induced ethyl methanesulfonate mutants uncovered by one of the largest deficiencies. No lethal mutation of the beta-gene was found.

Quantitative analysis of the amount of larval serum protein-1 (LSP-1) synthesized by flies with different doses of the LSP-1 coding sequences.

Larval serum protein-1 (LSP-1) and LSP-2 are the major proteins of Drosophila larval serum. The amount of LSP-1 synthesized is strictly proportional to the number of LSP-1 genes present within the range 1-10. The normal number in female flies is 6. Flies with extreme amounts of LSP-1 were, by our criteria, as fit as the wild type. The ratio of LSP-2:LSP-1 was analyzed in 169 different stocks and was constant in 164 of these. The significantly different ratios in five stocks were all due to the lack of one of the LSP-1 gene products.

Regulation of synthesis of the larval serum proteins of Drosophila melanogaster.

We have determined the relative amounts of subunits of larval serum proteins (LSPs) 1 and 2 during larval development in Drosophila melanogaster. These results indicate that synthesis of polypeptide subunits of LSP-1 and LSP-2 is coordinate: the proteins are first detected at the same time; they accumulate in a coordinate fashion; their RNAs are first detected at the same time; the RNAs also accumulate in similar relative amounts. Analyses of fat body polypeptides and fat body RNA indicate that synthesis of LSP-1 declines at a time when there are still substantial quantities of LSP-1 RNA in the cytoplasm. Cessation of LSP-1 subunit synthesis occurs before cessation of LSP-2 synthesis, indicating that at late times the genes (or mRNAs) for these two proteins are subject to different "switch-off" controls.

Binding of bacterial lipopolysaccharide to murine lymphocytes.

Does LPS activate lymphocytes by binding to a specific cell-surface receptor or by nonspecific hydrophobic interaction with the plasma membrane? We examined this question by detecting cell-bound LPS using immunofluorescence microscopy and radiobinding techniques. LPS binding to splenic lymphocytes from C3H/St mice has characteristics of specific binding: saturability with respect to dose and time, selectivity for a subclass of B-cells, and a correlation between binding and mitogenesis. 125I-labeled LPS bound to cells and analyzed quantitatively by SDS-PAGE separated into 3 major components: peaks 1, 2, and 3 (1 equals the fastest moving). Lymphocytes preferentially bound peak 1, murine RBC peaks 1 and 2, and macrophages peak 2. In contrast, specific antibody preferred peaks 2 and 3. Differential staining of gels suggested that peak 3 is carbohydrate-rich and peak 1 is lipid-rich. LPS was released from these cells at different rates. We conclude that selectivity of LPS binding may be reflected in preferential binding of LPS subunits of different size and/or composition, as well as differential retention of bound LPS.