Restricted Ig variable region gene expression among Ly-1+ B cell lymphomas

The majority of the characterized Ly-1+ B cell lymphomas of B10.H-2aH-4bp/Wts origin (the CH series) bear surface Ig related by Ag specificity or idiotype or both. To determine the genetic basis for these structural similarities, we have sequenced the VH and VL region genes expressed by 10 CH lymphomas, and have compared their VH and V kappa gene rearrangements by Southern blot analysis to one another and to those of four other CH lymphomas. Sequence analysis identified only five different VH, and seven different VL genes, and indicated that these V genes are essentially unmutated. CH lymphomas which express the identical VH gene share at least one idiotope. Thus, the basis for shared idiotype and specificity is due in most cases to the use of the same V gene. This restriction in V gene expression is not due to the preferential use of V genes of any particular VH family or VL group, as the expressed V genes belong to four different VH families and four V kappa groups, and include V lambda 1 and V lambda 2. We hypothesize that Ag selection accounts for the restriction in V gene usage among CH lymphomas.     

Rib cage and abdominal expiratory muscle responses to CO2 and esophageal distension

The present study compared the responses of rib cage and abdominal expiratory muscles to chemical and mechanical stimuli. In pentobarbital-anesthetized spontaneously breathing dogs, electromyograms (EMG) were recorded from the triangularis sterni (TS) and transverse abdominis (TA) muscles using bipolar intramuscular wire electrodes. During resting oxygen breathing, both muscles were electrically active during expiration. Progressive hyperoxic hypercapnia significantly augmented the expiratory activity of both the TA and the TS. However, the mean percent increases in electrical activity in response to CO2 were substantially greater for the TA than for the TS at all PCO2 levels greater than 50 Torr (P less than 0.01). Occlusion of the airway at end inspiration significantly delayed the onset of TS EMG (from 0.35 +/- 0.07 to 3.35 +/- 0.67 sec; P less than 0.002) and decreased TS EMG rate of rise (P less than 0.002), but did not significantly alter these parameters for the TA. Esophageal distension increased TS EMG in all dogs (by mean of 220 +/- 64%; P less than 0.01), but in contrast decreased TA EMG in all dogs (by a mean of 63 +/- 12%; P less than 0.001). The response to esophageal distention occurred in a graded manner and appeared to be mediated predominantly via vagal afferents. We concluded that expiratory muscles of the rib cage and abdomen manifest substantial differences in their electrical responses to chemoreceptor, pulmonary stretch receptor, and esophageal mechanoreceptor stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cellular and molecular markers of anteroposterior and dorsoventral organisation in the vitellogenic follicles of adult Sarcophaga bullata (Diptera) and dorsoventral orientation of follicles in the ovary

Summary Polar organisation in the follicles of adult Sarcophaga bullata is reflected in the nurse cell-oocyte axis and in the orientation of the two polar cell pairs in the follicular epithelium. The internal organisation of the nurse cell chamber contributes to polarity but not to dorsoventral asymmetry. Dorsoventral asymmetry is correlated with the eccentric position of the germinal vesicle and the orientation of the polar cell pairs; no other follicle cell specialisations are seen. In an ovary, follicles are preferentially orientated with the dorsal side to the centre of the ovary. Cytoskeletal and some haemolymph proteins are molecular markers of polarity. Thus, in pre-vitellogenic stages, tubulin immunoreactivity is higher in the oocyte than in the nurse cells, actin immunoreactivity is the same over the cystocytes and larval serum proteins are restricted to the poles. During vitellogenesis, both actin and tubulin become more concentrated in the nurse cells and larval serum protein 1 accumulated in the polar cells during border cell migration when yolk polypeptides also accumulate in the oocyte. At the end of vitellogenesis a lipophorin is taken up by the oocyte. No molecular marker of dorsoventral asymmetry was identified.     

Regulation of ACV synthetase activity in the beta-lactam biosynthetic pathway by carbon sources and their metabolites

The activity of -l--aminoadipyl)-l-cysteinyl-d-valine catalysis. Addition of l-cysteine to fermentation media increased -lactam production in both organisms and alleviated the negative carbon source regulation by glycerol in S. clavuligerus.     

Serial studies of autologous antibody reactivity to squamous cell carcinoma of the head and neck

Summary In previous studies we evaluated the incidence and specificity of autologous antibody reactivity against squamous cell carcinoma of the head and neck (SCCHN). We were able to demonstrate that autologous antibody reactivity is present in native sera but was usually of too low a titer to allow further analysis. Dissociation of immune complexes by acidification and ultrafiltration of serum augmented autologous antibody reactivity in nine out of nine autologous systems tested. Native antibody and antibody derived from immune complexes produced by the host and reactive with autologous tumor cells may be directed against physiologically relevant antigens. Therefore, correlations of antibody titers with clinical course may provide insight into the nature of the host response to cancer. In the present analysis, serological studies of six patients with SCCHN were performed with serum samples obtained over many months. Results of serial serological assays were correlated to tumor progression and clinical course. Fluctuations in autologous antibody reactivity were noted over time. In four cases, rises in autologous antibody titers preceded the clinical diagnosis of recurrence by several months. Drops in autologous antibody reactivity were noted in two cases following surgery or radiation therapy. In two cases of long-term survivors, no correlation between antibody reactivity and clinical course was noted. Specificity analysis of the six autologous systems demonstrated reactivity against autologous and allogeneic SCCHN as well as melanoma cell lines. These sera did not react with glioma, neuroblastoma, renal cell, breast, bladder and colon carcinoma cell lines nor with fetal calf serum, pooled lymphocytes, red blood cells and platelets. Autologous serial serological studies may provide a means by which to evaluate the host/tumor relationship in patients with SCCHN.     

Effects of cyclic AMP and butyrate on cell cycle,DNA, RNA,and purine synthesis of cultured astrocytes

Dibutyryl cyclic monophosphate (dBcAMP) has been shown to inhibit growth, and alter the morphology of astrocytes. However, the potential contribution of its hydrolytic product, butyrate, in inducing some of the changes that have been attributed to dBcAMP, is not clear. DNA, RNA, and purine synthesis were therefore studied in primary astrocyte cultures after 24 hours of exposure to varying concentrations of butyrate, dBcAMP, and agents that increase intracellular cAMP levels. Progression of cells through cell cycle was also studied by flow cytometry. Dibutyryl cAMP partially arrested cells in Go/G1 phase of cell cycle while sodium butyrate increased the percentage population of cells in G2/M phase. DNA synthesis and de novo purine synthesis were inhibited after treatment with dBcAMP, sodium butyrate, and various drugs that increase intracellular cAMP levels. RNA synthesis was increased with cAMP but was not affected by sodium butyrate. Our study shows that at millimolar concentrations, butyrate is capable of altering the cell cycle and inhibiting DNA synthesis in primary astrocyte cultures, in a manner that is similar although not identical to the effects of dBcAMP.     

The effect of dissolved oxygen on the growth of young-of-the-year winter flounder,Pseudopleuronectes americanus

Synopsis The effects of constant and diurnally fluctuating levels of dissolved oxygen on the growth of young-of-the-year winter flounder,Pseudopleuronectes americanus, were examined under controlled laboratory conditions. Fish were exposed for either 10 or 11 weeks to constant levels of 6.7 (high) and 2.2 (low) mg l^–1, and a diurnal fluctuation, ranging from 2.5 to 6.4 mg 0₂l^–1. Growth rates, calculated for both standard length and weight, for fish exposed to low and diurnally fluctuating levels were significantly reduced (p < 0.001) as compared to those for fish exposed to the high level. Growth rates of fish exposed to the high level were over twice those of fish held under low oxygen conditions. Under fluctuating conditions, fish grew at intermediate rates. Following these exposures, all fish were subsequently held at 7.2 mg Oz l^–1 for five weeks. Growth rates increased over two and a half times for fish previously exposed to the low oxygen level and were significantly (p < 0.001) higher than for the other two groups.     

Management of the recalcitrant total-hip arthroplasty wound

The infection rate for total-hip arthroplasty is around 1 percent. This small group is usually managed by complete removal of the prosthesis and the cement and closure over suction catheters to "collapse" the wound and eventually achieve a girdlestone arthroplasty. Occasionally, there are patients who have a persistent draining wound after this treatment and repeated efforts at wound closure. We present 27 patients who had recalcitrant, noncollapsible wounds of the hip that were present for many months to years. Twenty-eight cases of infected total-hip arthroplasties that did not respond to removal of the prosthesis and cement and closure were seen by the authors between January of 1977 and December of 1988. One patient had bilateral involvement. Average age was 64 years (range 33 to 79 years). There was an average of 4.2 previous surgical attempts at closure (range 1 to 21). Staphylococcus aureus was the most common organism, but the infections were virtually all multiple. Thirty-three muscles were utilized in 27 patients. The rectus femoris was used in 23 cases, the vastus lateralis in 8, tensor fasciae latae in 1, and combined latissimus dorsi-serratus anterior free-tissue transfers were carried out in 2. Multiple combinations of transpositions and free flaps were utilized. Follow-up ranged from 1 to 10 years, with an average of 6.4 years. Eighteen patients were ambulatory with minor degrees of pain, five ambulated with a cane, seven ambulated with a walker, six ambulated with crutches, and four ambulated unassisted, all of whom had reimplantation of their hip arthroplasty at least 12 months following the muscle flap procedure.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vitro effects of arachidonic acid on the prostaglandin synthesizing system in gastric mucosa

Self-destruction of the prostaglandin cyclooxygenase has been suggested to be an important factor in the regulation of endogenous prostaglandin synthesis. The present study was done in order to define the role of this substrate-induced inactivation in the regulation of prostaglandin synthesis in gastric mucosa. In tissue homogenate, the prostaglandin synthesizing capacity is rapidly inactivated at 37 degrees C, even in the absence of exogenous arachidonic acid. It was shown that this inactivation can be prevented both by EDTA as a chelator of calcium-ions and by tetracaine, a specific inhibitor of the phospholipase A2. Additional exogenous arachidonic acid again inactivated prostaglandin synthesis in a dose dependent manner. In contrast, the prostaglandin synthesizing capacity in organ cultured mucosal biopsies is well preserved, although the release of endogenous substrate was activated by extracellular calcium and Ca-ionophore A23187. Furthermore, even at high concentrations of exogenous arachidonic acid present in the culture medium, the synthesizing capacity in intact biopsies was only slightly and reversibly reduced. These large differences between intact biopsies and cell free tissue preparations point to very efficient mechanisms controlling the substrate availability for the cyclooxygenase system both from endogenous and exogenous sources in intact gastric mucosa.     

Combination biotherapy utilizing interleukin-2 and alpha interferon in patients with advanced cancer: a National Biotherapy Study Group Trial.

The National Biotherapy Study Group (NBSG) conducted a broad phase II trial using interleukin-2 (IL-2) by continuous infusion and alpha interferon (IFN) subcutaneously in 267 patients with a variety of advanced cancers, including 29 with breast cancer, 89 with renal cancer, and 69 with melanoma. IL-2 [18 million international units (MIU)/m2] was given by continuous infusion for 108 hours with 3 mu/m2 subcutaneous IFN every other day during the IL-2 infusion. The patients were treated for 1 week followed by a 2-week rest. After two cycles of treatment, patients were evaluated for response. Of the 237 patients evaluable for response, 20 (8%) had a complete or partial response and 128 (54%) were stable. Therefore, 62% of the evaluable patients were nonprogressive during the first 90 days of IL-2/IFN therapy. The objective response rate was 11% in melanoma, 7% in renal cancer, 14% in breast cancer, and 3% in patients with a variety of malignancies for an overall response rate of 7% in these patients with advanced cancer. The patients were treated on a general medical ward and tolerated treatment well with fatigue and fever being nearly universal. Dyspnea, pruritus, chills, and elevated creatinines were frequent but less common. This combination biotherapy regimen has minimal activity in a variety of advanced cancers and must be compared with the best existing chemotherapy for each cancer type in randomized, prospective trials.